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Many cancers reduce oxygen to protect themselves in 6 ways. Vitamin D stops all 6 ways – March 2022


Vitamin D and Hypoxia: Points of Interplay in Cancer

Cancers (Basel). 2022 Mar 31;14(7):1791. doi: 10.3390/cancers14071791.
Ioanna-Maria Gkotinakou 1, Ilias Mylonis 1, Andreas Tsakalof 1

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Vitamin D is a hormone that, through its action, elicits a broad spectrum of physiological responses ranging from classic to nonclassical actions such as bone morphogenesis and immune function. In parallel, many studies describe the antiproliferative, proapoptotic, antiangiogenic effects of calcitriol (the active hormonal form) that contribute to its anticancer activity. Additionally, epidemiological data signify the inverse correlation between vitamin D levels and cancer risk. On the contrary, tumors possess several adaptive mechanisms that enable them to evade the anticancer effects of calcitriol. Such maladaptive processes are often a characteristic of the cancer microenvironment, which in solid tumors is frequently hypoxic and elicits the overexpression of Hypoxia-Inducible Factors (HIFs). HIF-mediated signaling not only contributes to cancer cell survival and proliferation but also confers resistance to anticancer agents. Taking into consideration that calcitriol intertwines with signaling events elicited by the hypoxic status cells, this review examines their interplay in cellular signaling to give the opportunity to better understand their relationship in cancer development and their prospect for the treatment of cancer.
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References
  • 1. Bouillon, R.; Carmeliet, G.; Verlinden, L.; van Etten, E.; Verstuyf, A.; Luderer, H.F.; Lieben, L.; Mathieu, C.; DeMay, M. Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice. Endocr. Rev. 2008,29, 726-776. [CrossRef] [PubMed]
  • 2. Zhang, R.; Naughton, D.P. Vitamin D in health and disease: Current perspectives. Nutr. J. 2010, 9, 65. [CrossRef] [PubMed]
  • 3. Bikle, D. Nonclassic Actions of Vitamin D. J. Clin. Endocrinol. Metab. 2009, 94, 26-34. [CrossRef] [PubMed]
  • 4. Bouillon, R.; Eelen, G.; Verlinden, L.; Mathieu, C.; Carmeliet, G.; Verstuyf, A. Vitamin D and cancer. J. Steroid Biochem. Mol. Biol. 2006,102,156-162. [CrossRef]
  • 5. Holick, M.F. Vitamin D deficiency. N. Engl. J. Med. 2007, 357, 266-281. [CrossRef]
  • 6. Masuda, S.; Jones, G. Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol. Cancer Ther. 2006,5, 797-808. [CrossRef]
  • 7. Bikle, D.D. Extraskeletal actions of vitamin D. Ann. N. Y. Acad. Sci. 2016,1376, 29-52. [CrossRef]
  • 8. Feldman, D.; Krishnan, A.V.; Swami, S.; Giovannucci, E.; Feldman, B.J. The role of vitamin D in reducing cancer risk and progression. Nat. Cancer 2014,14, 342-357. [CrossRef]
  • 9. Holick, M.F. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am. J. Clin. Nutr. 2004, 80,1678S-1688S. [CrossRef]
  • 10. Wang, H.; Chen, W.; Li, D.; Yin, X.; Zhang, X.; Olsen, N.; Zheng, S.G. Vitamin D and Chronic Diseases. Aging Dis. 2017, 8, 346-353. [CrossRef]
  • 11. Garland, C.; Garland, F.C.; Shaw, E.; Comstock, G.W.; Helsing, K.J.; Gorham, E.D. Serum 25-Hydroxyvitamin D and Colon Cancer: Eight-Year Prospective Study. Lancet 1989, 334,1176-1178. [CrossRef]
  • 12. Engel, P.; Fagherazzi, G.; Boutten, A.; Dupre, T.; Mesrine, S.; Boutron-Ruault, M.-C.; Clavel-Chapelon, F. Serum 25(OH) Vitamin D and Risk of Breast Cancer: A Nested Case-Control Study from the French E3N Cohort. Cancer Epidemiol. Biomark. Prev. 2010,19, 2341-2350. [CrossRef]
  • 13. Ahonen, M.H.; Tenkanen, L.; Teppo, L.; Hakama, M.; Tuohimaa, P. Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes Control 2000,11, 847-852. [CrossRef]
  • 14. Tretli, S.; Hernes, E.; Berg, J.P.; Hestvik, U.E.; Robsahm, T.E. Association between serum 25(OH)D and death from prostate cancer. Br. J. Cancer 2009,100, 450-454. [CrossRef]
  • 15. Giovannucci, E.; Liu, Y.; Rimm, E.B.; Hollis, B.W.; Fuchs, C.S.; Stampfer, M.J.; Willett, W.C. Prospective Study of Predictors of Vitamin D Status and Cancer Incidence and Mortality in Men. J. Natl. Cancer Inst. 2006, 98, 451-459. [CrossRef]
  • 16. Fleet, J.C.; Desmet, M.; Johnson, R.; Li, Y. Vitamin D and cancer: A review of molecular mechanisms. Biochem. J. 2011, 441, 61-76. [CrossRef]
  • 17. Giammanco, M.; Di Majo, D.; La Guardia, M.; Aiello, S.; Crescimannno, M.; Flandina, C.; Tumminello, F.M.; Leto, G. Vitamin D in cancer chemoprevention. Pharm. Biol. 2015, 53,1399-1434. [CrossRef]
  • 18. Ma, Y.; Trump, D.L.; Johnson, C.S. Vitamin D in combination cancer treatment. J. Cancer 2010,1,101-107. [CrossRef]
  • 19. Mehta, R.G.; Peng, X.; Alimirah, F.; Murillo, G.; Mehta, R. Vitamin D and breast cancer: Emerging concepts. Cancer Lett. 2013, 334, 95-100. [CrossRef]
  • 20. Angeli-Terzidou, A.E.; Gkotinakou, I.-M.; Pazaitou-Panayiotou, K.; Tsakalof, A. Inhibition of calcitriol inactivating enzyme CYP24A1 gene expression by flavonoids in hepatocellular carcinoma cells under normoxia and hypoxia. Arch. Biochem. Biophys. 2021, 704,108889. [CrossRef]
  • 21. Semenza, G.L. The Genomics and Genetics of Oxygen Homeostasis. Annu. Rev. Genom. Hum. Genet. 2020, 21,183-204. [CrossRef]
  • 22. Mylonis, I.; Simos, G.; Paraskeva, E. hypoxia-Inducible Factors and the Regulation of Lipid Metabolism. Cells 2019, 8, 214. [CrossRef]
  • 23. Schito, L.; Semenza, G.L. hypoxia-Inducible Factors: Master Regulators of Cancer Progression. Trends Cancer 2016, 2, 758-770. [CrossRef]
  • 24. Triantafyllou, A.; Mylonis, I.; Simos, G.; Bonanou, S.; Tsakalof, A. Flavonoids induce HIF-1a but impair its nuclear accumulation and activity. Free Radic. Biol. Med. 2008, 44, 657-670. [CrossRef]
  • 25. Mylonis, I.; Chachami, G.; Simos, G. Specific Inhibition of HIF Activity: Can Peptides Lead the Way? Cancers 2021, 13, 410. [CrossRef]
  • 26. Zhong, J.-C.; Li, X.-B.; Lyu, W.-Y.; Ye, W.-C.; Zhang, D.-M. Natural products as potent inhibitors of hypoxia-inducible factor-1a in cancer therapy. Chin. J. Nat. Med. 2020,18, 696-703. [CrossRef]
  • 27. Choudhry, H.; Harris, A.L. Advances in hypoxia-Inducible Factor Biology. Cell Metab. 2018,27, 281-298. [CrossRef]
  • 28. Pinto, J.T.; Cooper, A.J.L. From Cholesterogenesis to Steroidogenesis: Role of Riboflavin and Flavoenzymes in the Biosynthesis of Vitamin D. Adv. Nutr. Int. Rev. J. 2014, 5,144-163. [CrossRef]
  • 29. Heaney, R.P. Vitamin D in Health and Disease. Clin. J. Am. Soc. Nephrol. 2008, 3,1535-1541. [CrossRef]
  • 30. Japelt, R.B.; Jakobsen, J. Vitamin D in plants: A review of occurrence, analysis, and biosynthesis. Front. Plant Sci. 2013, 4,136. [CrossRef] [PubMed]
  • 31. Jones, G.; Prosser, D.E.; Kaufmann, M. Cytochrome P450-mediated metabolism of vitamin D. J. Lipid Res. 2014,55,1331. [CrossRef] [PubMed]
  • 32. Schuster, I. Cytochromes P450 are essential players in the vitamin D signaling system. Biochim. Biophys. Acta 2011,1814,186-199. [CrossRef] [PubMed]
  • 33. Bikle, D.D. Vitamin D Metabolism, Mechanism of Action, and Clinical Applications. Chem. Biol. 2014, 21, 319-329. [CrossRef]
  • 34. Masuda, S.; Byford, V.; Arabian, A.; Sakai, Y.; Demay, M.B.; St-Arnaud, R.; Jones, G. Altered Pharmacokinetics of 1a,25-Dihydroxyvitamin D3and 25-Hydroxyvitamin D3in the Blood and Tissues of the 25-Hydroxyvitamin D-24-Hydroxylase (Cyp24a1) Null Mouse. Endocrinology 2005,146, 825-834. [CrossRef]
  • 35. St-Arnaud, R.; Arabian, A.; Travers, R.; Barletta, F.; Raval-Pandya, M.; Chapin, K.; Depovere, J.; Mathieu, C.; Christakos, S.; DeMay, M.B.; et al. Deficient Mineralization of Intramembranous Bone in Vitamin D-24-Hydroxylase-Ablated Mice Is Due to Elevated 1,25-Dihydroxyvitamin D and Not to the Absence of 24,25-Dihydroxyvitamin D*. Endocrinology 2000,141, 2658-2666. [CrossRef]
  • 36. Slominski, A.; Semak, I.; Zjawiony, J.; Wortsman, J.; Li, W.; Szczesniewski, A.; Tuckey, R.C. The cytochrome P450scc system opens an alternate pathway of vitamin D3 metabolism. FEBS J. 2005, 272, 4080-4090. [CrossRef]
  • 37. Slominski, A.; Zmijewski, M.; Semak, I.; Zbytek, B.; Pisarchik, A.; Li, W.; Zjawiony, J.; Tuckey, R. Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways. Anti Cancer Agents Med. Chem. 2014,14, 77-96. [CrossRef]
  • 38. Slominski, A.T.; Brozyna, A.; Skobowiat, C.; Zmijewski, M.; Kim, T.-K.; Janjetovic, Z.; Oak, A.S.; Jozwicki, W.; Jetten, A.; Mason, R.; et al. On the role of classical and novel forms of vitamin D in melanoma progression and management. J. Steroid Biochem. Mol. Biol. 2018,177,159-170. [CrossRef]
  • 39. Slominski, A.T.; Brozyna, A.A.; Zmijewski, M.A.; Janjetovic, Z.; Kim, T.-K.; Slominski, R.M.; Tuckey, R.C.; Mason, R.S.; Jetten, A.M.; Guroji, P.; et al. The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers. Adv. Exp. Med. Biol. 2020,1268, 257-283. [CrossRef]
  • 40. Tongkao-On, W.; Carter, S.; Reeve, V.E.; Dixon, K.M.; Gordon-Thomson, C.; Halliday, G.M.; Tuckey, R.C.; Mason, R.S. CYP11A1 in skin: An alternative route to photoprotection by vitamin D compounds. J. Steroid Biochem. Mol. Biol. 2015,148, 72-78. [CrossRef]
  • 41. Jones, G.; Prosser, D.E.; Kaufmann, M. 25-Hydroxyvitamin D-24-hydroxylase (CYP24A1): Its important role in the degradation of vitamin D. Arch. Biochem. Biophys. 2012, 523, 9-18. [CrossRef]
  • 42. Zierold, C.; Darwish, H.M.; DeLuca, H.F. Two vitamin D response elements function in the rat 1,25-dihydroxyvitamin D 24-hydroxylase promoter. J. Biol. Chem. 1995, 270,1675-1678. [CrossRef]
  • 43. Meyer, M.B.; Goetsch, P.D.; Pike, J.W. A Downstream Intergenic Cluster of Regulatory Enhancers Contributes to the Induction of CYP24A1 Expression by 1 a,25-Dihydroxyvitamin D3. J. Biol. Chem. 2010,285,15599-15610. [CrossRef]
  • 44. Khundmiri, S.J.; Murray, R.D.; Lederer, E. PTH and Vitamin D. Compr. Physiol. 2016, 6, 561-601.
  • 45. Rost, C.R.; Bikle, D.D.; Kaplan, R.A. In Vitro Stimulation of 25-Hydroxycholecalciferol la- Hydroxylation by Parathyroid Hormone in Chick Kidney Slices: Evidence for a Role for Adenosine 3',5'- Monophosphate *. Endocrinology 1981,108,1002-1006. [CrossRef]
  • 46. Zierold, C.; Mings, J.A.; DeLuca, H.F. Parathyroid hormone regulates 25-hydroxyvitamin D3-24-hydroxylase mRNA by altering its stability. Proc. Natl. Acad. Sci. USA 2001, 98,13572-13576. [CrossRef]
  • 47. Perwad, F.; Zhang, M.Y.H.; Tenenhouse, H.S.; Portale, A.A. Fibroblast growth factor 23 impairs phosphorus and vitamin D metabolism in vivo and suppresses 25-hydroxyvitamin D-1 a-hydroxylase expression in vitro. Am. J. Physiol. Physiol. 2007, 293, F1577-F1583. [CrossRef] [PubMed]
  • 48. Haussler, M.R.; Jurutka, P.W.; Mizwicki, M.; Norman, A.W. Vitamin D Receptor (VDR)-mediated actions of 1a,25(OH)2 vitamin D3 : Genomic and non-genomic mechanisms. Best. Pract. Res. Clin. Endocrinol. Metab. 2011,25, 543-559. [CrossRef] [PubMed]
  • 49. Haussler, M.R.; Whitfield, G.K.; Kaneko, I.; Haussler, C.A.; Hsieh, D.; Hsieh, J.-C.; Jurutka, P.W. Molecular Mechanisms of Vitamin D Action. Calcif. Tissue Int. 2013, 92, 77-98. [CrossRef]
  • 50. Pike, J.W.; Meyer, M.B. Fundamentals of vitamin D hormone-regulated gene expression. J. Steroid Biochem. Mol. Biol. 2013,144, 5-11. [CrossRef] [PubMed]
  • 51. Duran, A.; Hernandez, E.D.; Reina-Campos, M.; Castilla, E.A.; Subramaniam, S.; Raghunandan, S.; Roberts, L.R.; Kisseleva, T.; Karin, M.; Diaz-Meco, M.T.; et al. p62/SQSTM1 by Binding to Vitamin D Receptor Inhibits Hepatic Stellate Cell Activity, Fibrosis, and Liver Cancer. Cancer Cell 2016, 30, 595-609. [CrossRef]
  • 52. Haberle, V.; Stark, A. Eukaryotic core promoters and the functional basis of transcription initiation. Nat. Rev. Mol. Cell Biol. 2018, 19, 621-637. [CrossRef]
  • 53. Carlberg, C.; Muñoz, A. An update on vitamin D signaling and cancer. Semin. Cancer Biol. 2020, 79, 217-230. [CrossRef]
  • 54. Seuter, S.; Neme, A.; Carlberg, C. Epigenome-wide effects of vitamin D and their impact on the transcriptome of human monocytes involve CTCF. Nucleic Acids Res. 2016, 44, 4090-4104. [CrossRef]
  • 55. Pereira, F.; Barbáchano, A.; Silva, J.; Bonilla, F.; Campbell, M.J.; Muñoz, A.; Larriba, M.J. KDM6B/JMJD3 histone deme-thylase is induced by vitamin D and modulates its effects in colon cancer cells. Hum. Mol. Genet. 2011, 20, 4655-4665. [CrossRef]
  • 56. Wei, Z.; Yoshihara, E.; He, N.; Hah, N.; Fan, W.; Pinto, A.F.; Huddy, T.; Wang, Y.; Ross, B.; Estepa, G.; et al. Vitamin D Switches BAF Complexes to Protect |3 Cells. Cell 2018,173,1135-1149.e15. [CrossRef]
  • 57. Chichiarelli, S.; Altieri, F.; Paglia, G.; Rubini, E.; Minacori, M.; Eufemi, M. ERp57/PDIA3: New insight. Cell. Mol. Biol. Lett. 2022, 27,12. [CrossRef]
  • 58. Kranz, P.; Neumann, F.; Wolf, A.; Classen, F.; Pompsch, M.; Ocklenburg, T.; Baumann, J.; Janke, K.; Baumann, M.; Goepelt, K.; et al. PDI is an essential redox-sensitive activator of PERK during the unfolded protein response (UPR). Cell Death Dis. 2017, 8, e2986. [CrossRef]
  • 59. Ivanova, I.G.; Park, C.V.; Yemm, A.I.; Kenneth, N.S. PERK/eIF2a signaling inhibits HIF-induced gene expression during the unfolded protein response via YB1-dependent regulation of HIF1a translation. Nucleic Acids Res. 2018, 46, 3878-3890. [CrossRef]
  • 60. Doroudi, M.; Schwartz, Z.; Boyan, B.D. Membrane-mediated actions of 1,25-dihydroxy vitamin D3: A review of the roles of phospholipase A2 activating protein and Ca2+/calmodulin-dependent protein kinase II. J. Steroid Biochem. Mol. Biol. 2015,147, 81-84. [CrossRef]
  • 61. Nemere, I.; Safford, S.E.; Rohe, B.; DeSouza, M.M.; Farach-Carson, M.C. Identification and characterization of 1,25D3-membrane-associated rapid response, steroid (1,25D3-MARRS) binding protein. J. Steroid Biochem. Mol. Biol. 2004, 89, 281-285. [CrossRef]
  • 62. Allison, M.W.; Robert, S.; Thao, T.; Michael, E.; Benjamin, K.; Meckling, K.A. Differential effects of the 1,25D3-MARRS Receptor (ERp57/PDIA3) on murine mammary gland development depend on the vitamin D3 dose. Steroids 2020,158,108621.
  • 63. Axanova, L.S.; Chen, Y.Q.; McCoy, T.; Sui, G.; Cramer, S.D. 1,25-dihydroxyvitamin D3 and PI3K/AKT inhibitors synergistically inhibit growth and induce senescence in prostate cancer cells. Prostate 2010, 70,1658-1671. [CrossRef]
  • 64. Nemere, I.; Garbi, N.; Winger, Q. The 1,25D3-MARRS Receptor /PDIA3/ERp57 and lifespan. J. Cell. Biochem. 2015,116, 380-385. [CrossRef]
  • 65. Buitrago, C.; Pardo, V.G.; Boland, R. Role of VDR in 1a,25-dihydroxyvitamin D3-dependent non-genomic activation of MAPKs, Src and Akt in skeletal muscle cells. J. Steroid Biochem. Mol. Biol. 2013,136,125-130. [CrossRef]
  • 66. Zhao, G.; Simpson, R.U. Membrane localization, Caveolin-3 association and rapid actions of vitamin D Receptor in cardiac myocytes. Steroids 2010, 75, 555-559. [CrossRef]
  • 67. Chen, J.; Doroudi, M.; Cheung, J.; Grozier, A.L.; Schwartz, Z.; Boyan, B.D. Plasma membrane Pdia3 and VDR interact to elicit rapid responses to 1a,25(OH)2D3. Cell. Signal. 2013,25,2362-2373. [CrossRef]
  • 68. Ema, M.; Taya, S.; Yokotani, N.; Sogawa, K.; Matsuda, Y.; Fujii-Kuriyama, Y. A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor lalpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc. Natl. Acad. Sci. USA 1997, 94, 4273-4278. [CrossRef]
  • 69. Gu, Y.Z.; Moran, S.M.; Hogenesch, J.B.; Wartman, L.; Bradfield, C.A. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha. Gene Exp. 1998, 7, 205-213.
  • 70. Semenza, G.L.; Wang, G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 1992,12, 5447-5454. [CrossRef]
  • 71. Arany, Z.; Huang, L.E.; Eckner, R.; Bhattacharya, S.; Jiang, C.; Goldberg, M.A.; Bunn, H.F.; Livingston, D.M. An essential role for p300/CBP in the cellular response to hypoxia. Proc. Natl. Acad. Sci. USA 1996, 93,12969-12973. [CrossRef] [PubMed]
  • 72. Manalo, D.J.; Rowan, A.; Lavoie, T.; Natarajan, L.; Kelly, B.D.; Ye, S.Q.; Garcia, J.G.N.; Semenza, G.L. Transcriptional regulation of vascular endothelial cell responses to hypoxia by HIF-1. Blood 2005,105, 659-669. [CrossRef] [PubMed]
  • 73. Dengler, V.L.; Galbraith, M.; Espinosa, J.M. Transcriptional regulation by hypoxia inducible factors. Crit. Rev. Biochem. Mol. Biol. 2014, 49,1-15. [CrossRef] [PubMed]
  • 74. Kim, L.C.; Simon, M.C. hypoxia-Inducible Factors in Cancer. Cancer Res. 2022, 82,195-196. [CrossRef] [PubMed]
  • 75. Taylor, S.E.; Bagnall, J.; Mason, D.; Levy, R.; Fernig, D.G.; See, V. Differential sub-nuclear distribution of hypoxia-inducible factors (HIF)-1 and -2 alpha impacts on their stability and mobility. Open Biol. 2016, 6,160195. [CrossRef]
  • 76. Menrad, H.; Werno, C.; Schmid, T.; Copanaki, E.; Deller, T.; Dehne, N.; Brüne, B. Roles of hypoxia-inducible factor-1alpha (HIF-1alpha) versus HIF-2alpha in the survival of hepatocellular tumor spheroids. Hepatology 2010, 51, 2183-2192. [CrossRef]
  • 77. Smythies, J.A.; Sun, M.; Masson, N.; Salama, R.; Simpson, P.D.; Murray, E.; Neumann, V.; Cockman, M.A.-O.; Choudhry, H.; Ratcliffe, P.A.-O.X.; et al. Inherent DNA-binding specificities of the HIF-1 a and HIF-2a transcription factors in chromatin. EMBO Rep. 2019, 20, e46401. [CrossRef]
  • 78. Albanese, A.; Daly, L.; Mennerich, D.; Kietzmann, T.; See, V. The Role of hypoxia-Inducible Factor Post-Translational Modifications in Regulating Its Localisation, Stability, and Activity. Int. J. Mol. Sci. 2020,22, 268. [CrossRef]
  • 79. Battello, N.; Zimmer, A.D.; Goebel, C.; Dong, X.; Behrmann, I.; Haan, C.; Hiller, K.; Wegner, A. The role of HIF-1 in oncostatin M-dependent metabolic reprogramming of hepatic cells. Cancer Metab. 2016, 4,3. [CrossRef]
  • 80. D'Ignazio, L.; Bandarra, D.; Rocha, S. NF-kB and HIF crosstalk in immune responses. FEBS J. 2016,283, 413-424. [CrossRef]
  • 81. Obacz, J.; Pastorekova, S.; Vojtesek, B.; Hrstka, R. Cross-talk between HIF and p53 as mediators of molecular responses to physiological and genotoxic stresses. Mol. Cancer 2013,12, 93. [CrossRef]
  • 82. Taylor, C.T. Interdependent roles for hypoxia inducible factor and nuclear factor-KB in hypoxic inflammation. J. Physiol. 2008, 586, 4055-4059. [CrossRef]
  • 83. Papadakis, A.I.; Paraskeva, E.; Peidis, P.; Muaddi, H.; Li, S.; Raptis, L.; Pantopoulos, K.; Simos, G.; Koromilas, A.E. eIF2a Kinase PKR Modulates the Hypoxic Response by Stat3-Dependent Transcriptional Suppression of HIF-1 a. Cancer Res. 2010, 70, 7820-7829. [CrossRef]
  • 84. Al Taleb, Z.; Petry, A.; Chi, T.F.; Mennerich, D.; Görlach, A.; Dimova, E.; Kietzmann, T. Differential transcriptional regulation of hypoxia-inducible factor-1a by arsenite under normoxia and hypoxia: Involvement of Nrf2. Klin. Wochenschr. 2016, 94,1153-1166. [CrossRef]
  • 85. Lacher, S.E.; Levings, D.; Freeman, S.; Slattery, M. Identification of a functional antioxidant response element at the HIF1A locus. Redox Biol. 2018,19, 401-411. [CrossRef]
  • 86. Frede, S.; Stockmann, C.; Freitag, P.; Fandrey, J. Bacterial lipopolysaccharide induces HIF-1 activation in human monocytes via p44/42 MAPK and NF-kappa, B. Biochem. J. 2006, 396, 517-527. [CrossRef]
  • 87. Rius, J.; Guma, M.; Schachtrup, C.; Akassoglou, K.; Zinkernagel, A.S.; Nizet, V.; Johnson, R.S.; Haddad, G.G.; Karin, M. NF-kB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1a. Nature 2008, 453,807-811. [CrossRef]
  • 88. Van Uden, P.; Kenneth, N.S.; Rocha, S. Regulation of hypoxia-inducible factor-1 a by NF-kB. Biochem. J. 2008, 412, 477-484. [CrossRef]
  • 89. BelAiba, R.S.; Bonello, S.; Zähringer, C.; Schmidt, S.; Hess, J.; Kietzmann, T.; Görlach, A. hypoxia Up-Regulates hypoxia-Inducible Factor-1 a Transcription by Involving Phosphatidylinositol 3-Kinase and Nuclear Factor kB in Pulmonary Artery Smooth Muscle Cells. Mol. Biol. Cell 2007,18, 4691-4697. [CrossRef]
  • 90. Tsapournioti, S.; Mylonis, I.; Hatziefthimiou, A.; Ioannou, M.G.; Stamatiou, R.; Koukoulis, G.K.; Simos, G.; Molyvdas, P.-A.; Paraskeva, E. TNFa induces expression of HIF-1 a mRNA and protein but inhibits hypoxic stimulation of HIF-1 transcriptional activity in airway smooth muscle cells. J. Cell Physiol. 2013,228,1745-1753. [CrossRef]
  • 91. Takeda, K.; Ho, V.C.; Takeda, H.; Duan, L.-J.; Nagy, A.; Fong, G.-H. Placental but Not Heart Defects Are Associated with Elevated hypoxia-Inducible Factor a Levels in Mice Lacking Prolyl Hydroxylase Domain Protein 2. Mol. Cell. Biol. 2006, 26, 8336-8346. [CrossRef]
  • 92. Cui, J.; Duan, B.; Zhao, X.; Chen, Y.; Sun, S.; Deng, W.; Zhang, Y.; Du, J.; Chen, Y.; Gu, L. MBD3 mediates epigenetic regulation on EPAS1 promoter in cancer. Tumor Biol. 2016, 37,13455-13467. [CrossRef]
  • 93. Mohlin, S.; Hamidian, A.; Von Stedingk, K.; Bridges, E.; Wigerup, C.; Bexell, D.; Pahlman, S. PI3K-mTORC2 but not PI3K-mTORC1 Regulates Transcription of HIF2A/EPAS1 and Vascularization in Neuroblastoma. Cancer Res. 2015, 75, 4617-4628. [CrossRef]
  • 94. Moniz, S.; Bandarra, D.; Biddlestone, J.; Campbell, K.; Komander, D.; Bremm, A.; Rocha, S. Cezanne regulates E2F1-dependent HIF2a expression. J. Cell Sci. 2015,128, 3082-3093. [CrossRef]
  • 95. Nakazawa, M.S.; Eisinger-Mathason, T.S.K.; Sadri, N.; Ochocki, J.D.; Gade, T.P.F.; Amin, R.K.; Simon, M.C. Epigenetic reexpression of HIF-2a suppresses soft tissue sarcoma growth. Nat. Commun. 2016, 7,10539. [CrossRef]
  • 96. Garcia, R.; Bowman, T.L.; Niu, G.; Yu, H.; Minton, S.; Muro-Cacho, C.A.; Cox, C.E.; Falcone, R.; Fairclough, R.; Parsons, S.; et al. Constitutive activation of Stat3 by the Src and JAK tyrosine kinases participates in growth regulation of human breast carcinoma cells. Oncogene 2001,20, 2499-2513. [CrossRef]
  • 97. So, J.Y.; Smolarek, A.K.; Salerno, D.M.; Maehr, H.; Uskokovic, M.; Liu, F.; Suh, N. Targeting CD44-STAT3 Signaling by Gemini Vitamin D Analog Leads to Inhibition of Invasion in Basal-Like Breast Cancer. PLoS ONE 2013, 8, e54020. [CrossRef] [PubMed]
  • 98. Park, M.R.; Lee, J.H.; Park, M.S.; Hwang, J.E.; Shim, H.J.; Cho, S.H.; Chung, I.-J.; Bae, W.K. Suppressive Effect of 19-nor-1 a-25-Dihydroxyvitamin D2 on Gastric Cancer Cells and Peritoneal Metastasis Model. J. Korean Med Sci. 2012, 27,1037-1043. [CrossRef] [PubMed]
  • 99. Krishnan, A.V.; Feldman, D. Molecular pathways mediating the anti-inflammatory effects of calcitriol: Implications for prostate cancer chemoprevention and treatment. Endocr. Relat. Cancer 2010,17, R19-R38. [CrossRef]
  • 100. Stio, M.; Martinesi, M.; Bruni, S.; Treves, C.; Mathieu, C.; Verstuyf, A.; d'Albasio, G.; Bagnoli, S.; Bonanomi, A.G. The Vitamin D analogue TX 527 blocks NF-kappaB activation in peripheral blood mononuclear cells of patients with Crohn's disease. J. Steroid Biochem. Mol. Biol. 2007,103, 51-60. [CrossRef] [PubMed]
  • 101. Sun, J.; Kong, J.; Duan, Y.; Szeto, F.L.; Liao, A.; Madara, J.L.; Li, Y.C. Increased NF-kappaB activity in fibroblasts lacking the vitamin D Receptor . Am. J. Physiol. Endocrinol. Metab. 2006, 291, E315-E322. [CrossRef]
  • 102. Yu, X.P.; Bellido, T.; Manolagas, S.C. Down-regulation of NF-kappa B protein levels in activated human lymphocytes by 1,25-dihydroxyvitamin D3. Proc. Natl. Acad. Sci. USA 1995, 92,10990-10994. [CrossRef]
  • 103. Chen, Y.; Zhang, J.; Ge, X.; Du, J.; Deb, D.K.; Li, Y.C. Vitamin D Receptor inhibits nuclear factor kB activation by interacting with IkB kinase |3 protein. J. Biol. Chem. 2013,288,19450-19458. [CrossRef]
  • 104. Riis, J.L.; Johansen, C.; Gesser, B.; Muller, K.; Larsen, C.G.; Kragballe, K.; Iversen, L. 1alpha,25(OH)(2)D(3) regulates NF-kappaB DNA binding activity in cultured normal human keratinocytes through an increase in IkappaBalpha expres-sion. Arch. Dermatol. Res. 2004, 296,195-202. [CrossRef]
  • 105. Karin, M.; Cao, Y.; Greten, F.R.; Li, Z.-W. NF-kappaB in cancer: From innocent bystander to major culprit. Nat. Rev. Cancer 2002, 2, 301-310. [CrossRef]
  • 106. DiDonato, J.A.; Mercurio, F.; Karin, M. NF-kB and the link between inflammation and cancer. Immunol. Rev. 2012, 246, 379-400. [CrossRef]
  • 107. Li, F.; Zhang, J.; Arfuso, F.; Chinnathambi, A.; Zayed, M.E.; Alharbi, S.A.; Kumar, A.P.; Ahn, K.S.; Sethi, G. NF-kB in cancer therapy. Arch. Toxicol. 2015, 89, 711-731. [CrossRef]
  • 108. Chung, I.; Han, G.; Seshadri, M.; Gillard, B.M.; Yu, W.-D.; Foster, B.A.; Trump, D.L.; Johnson, C.S. Role of Vitamin D Receptor in the Antiproliferative Effects of Calcitriol in Tumor-Derived Endothelial Cells and Tumor AngiogenesisIn vivo. Cancer Res. 2009, 69, 967-975. [CrossRef]
  • 109. Dai, Y.; Zhang, J.; Xiang, J.; Li, Y.; Wu, D.; Xu, J. Calcitriol inhibits ROS-NLRP3-IL-113 signaling axis via activation of Nrf2-antioxidant signaling in hyperosmotic stress stimulated human corneal epithelial cells. Redox Biol. 2019, 21,101093. [CrossRef]
  • 110. Bardos, J.I.; Ashcroft, M. Negative and positive regulation of HIF-1: A complex network. Biochim. Biophys. Acta 2005, 1755, 107-120. [CrossRef]
  • 111. Akeno, N.; Robins, J.; Zhang, M.; Czyzyk-Krzeska, M.F.; Clemens, T.L. Induction of Vascular Endothelial Growth Factor by IGF-I in Osteoblast-Like Cells Is Mediated by the PI3K Signaling Pathway through the hypoxia-Inducible Factor-2 a. Endocrinology 2002,143, 420-425. [CrossRef] [PubMed]
  • 112. Guertin, D.A.; Sabatini, D.M. Defining the Role of mTOR in Cancer. Cancer Cell 2007,12, 9-22. [CrossRef] [PubMed]
  • 113. Nayak, B.K.; Feliers, D.; Sudarshan, S.; Friedrichs, W.E.; Day, R.T.; New, D.D.; Fitzgerald, J.P.; Eid, A.; DeNapoli, T.; Parekh, D.J.; et al. Stabilization of HIF-2a through redox regulation of mTORC2 activation and initiation of mRNA translation. Oncogene 2013, 32, 3147-3155. [CrossRef] [PubMed]
  • 114. Toschi, A.; Lee, E.; Gadir, N.; Ohh, M.; Foster, D.A. Differential Dependence of hypoxia-inducible Factors 1a and 2a on mTORC1 and mTORC2. J. Biol. Chem. 2008,283, 34495-34499. [CrossRef]
  • 115. Proietti, S.; Cucina, A.; D'Anselmi, F.; Dinicola, S.; Pasqualato, A.; Lisi, E.; Bizzarri, M. Melatonin and vitamin D3 synergisti-cally down-regulate Akt and MDM2 leading to TGF|3-1-dependent growth inhibition of breast cancer cells. J. Pineal. Res. 2011, 50, 150-158.
  • 116. Gkotinakou, I.-M.; Kechagia, E.; Pazaitou-Panayiotou, K.; Mylonis, I.; Liakos, P.; Tsakalof, A. Calcitriol Suppresses HIF-1 and HIF-2 Transcriptional Activity by Reducing HIF-1/2a Protein Levels via a VDR-Independent Mechanism. Cells 2020, 9, 2440. [CrossRef]
  • 117. Abu El Maaty, M.A.; Wolfl, S. Vitamin D as a Novel Regulator of Tumor Metabolism: Insights on Potential Mechanisms and Implications for Anti-Cancer Therapy. Int. J. Mol. Sci. 2017,18, 2184. [CrossRef]
  • 118. Jin, H.-O.; Seo, S.-K.; Kim, Y.-S.; Woo, S.-H.; Lee, K.-H.; Yi, J.-Y.; Lee, S.-J.; Choe, T.-B.; Lee, J.-H.; An, S.; et al. TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1. Oncogene 2011, 30, 3792-3801. [CrossRef]
  • 119. Horak, P.; Crawford, A.R.; Vadysirisack, D.D.; Nash, Z.M.; DeYoung, M.P.; Sgroi, D.; Ellisen, L.W. Negative feedback control of HIF-1 through REDD1-regulated ROS suppresses tumorigenesis. Proc. Natl. Acad. Sci. USA 2010,107, 4675-4680. [CrossRef]
  • 120. Flügel, D.; Görlach, A.; Michiels, C.; Kietzmann, T. Glycogen Synthase Kinase 3 Phosphorylates hypoxia-Inducible Factor 1a and Mediates Its Destabilization in a VHL-Independent Manner. Mol. Cell. Biol. 2007,27, 3253-3265. [CrossRef]
  • 121. Mottet, D.; Dumont, V.; Deccache, Y.; Demazy, C.; Ninane, N.; Raes, M.; Michiels, C. Regulation of hypoxia-inducible factor-1alpha protein level during hypoxic conditions by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta pathway in HepG2 cells. J. Biol. Chem. 2003, 278, 31277-31285. [CrossRef]
  • 122. Flügel, D.; Görlach, A.; Kietzmann, T. GSK-3ß regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1a. Blood 2012,119,1292-1301. [CrossRef]
  • 123. González-Sancho, J.M.; Larriba, M.J.; Muñoz, A. Wnt and Vitamin D at the Crossroads in Solid Cancer. Cancers 2020,12, 3434. [CrossRef]
  • 124. Xu, D.; Yao, Y.; Lu, L.; Costa, M.; Dai, W. Plk3 Functions as an Essential Component of the hypoxia Regulatory Pathway by Direct Phosphorylation of HIF-1 a. J. Biol. Chem. 2010,285,38944-38950. [CrossRef]
  • 125. Bullen, J.W.; Tchernyshyov, I.; Holewinski, R.J.; DeVine, L.; Wu, F.; Venkatraman, V.; Kass, D.L.; Cole, R.N.; Van Eyk, J.; Semenza, G.L. Protein kinase A—Dependent phosphorylation stimulates the transcriptional activity of hypoxia-inducible factor 1. Sci. Signal. 2016, 9, ra56. [CrossRef]
  • 126. Hubbi, M.E.; Gilkes, D.M.; Hu, H.; Kshitiz; Ahmed, I.; Semenza, G.L. Cyclin-dependent kinases regulate lysosomal degradation of hypoxia-inducible factor 1a to promote cell-cycle progression. Proc. Natl. Acad. Sci. USA 2014,111, E3325-E3334. [CrossRef]
  • 127. Warfel, N.A.; Dolloff, N.G.; Dicker, D.T.; Malysz, J.; El-Deiry, W.S. CDK1 stabilizes HIF-1 a via direct phosphorylation of Ser668 to promote tumor growth. Cell Cycle 2013,12, 3689-3701. [CrossRef]
  • 128. Peehl, D.M.; Shinghal, R.; Nonn, L.; Seto, E.; Krishnan, A.V.; Brooks, J.D.; Feldman, D. Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis. J. Steroid Biochem. Mol. Biol. 2004, 92,131-141. [CrossRef]
  • 129. Swami, S.; Raghavachari, N.; Muller, U.R.; Bao, Y.P.; Feldman, D. Vitamin D Growth Inhibition of Breast Cancer Cells: Gene Expression Patterns Assessed by cDNA Microarray. Breast Cancer Res. Treat. 2003, 80, 49-62. [CrossRef]
  • 130. Gradin, K.; Takasaki, C.; Fujii-Kuriyama, Y.; Sogawa, K. The Transcriptional Activation Function of the HIF-like Factor Requires Phosphorylation at a Conserved Threonine. J. Biol. Chem. 2002, 277, 23508-23514. [CrossRef]
  • 131. Lancaster, D.E.; McNeill, L.A.; McDonough, M.A.; Aplin, R.T.; Hewitson, K.S.; Pugh, C.W.; Ratcliffe, P.J.; Schofield, C.J. Disruption of dimerization and substrate phosphorylation inhibit factor inhibiting hypoxia-inducible factor (FIH) activity. Biochem. J. 2004, 383, 429-437. [CrossRef] [PubMed]
  • 132. Luo, W.; Yu, W.-D.; Ma, Y.; Chernov, M.; Trump, D.L.; Johnson, C.S. Inhibition of Protein Kinase CK2 ReducesCyp24a1Expression and Enhances 1,25-Dihydroxyvitamin D3Antitumor Activity in Human Prostate Cancer Cells. Cancer Res. 2013, 73, 2289-2297. [CrossRef] [PubMed]
  • 133. Pangou, E.; Befani, C.; Mylonis, I.; Samiotaki, M.; Panayotou, G.; Simos, G.; Liakos, P. HIF-2a phosphorylation by CK1delta promotes erythropoietin secretion in liver cancer cells under hypoxia. J. Cell Sci. 2016,129, 4213-4226. [CrossRef] [PubMed]
  • 134. Kalousi, A.; Mylonis, I.; Politou, A.S.; Chachami, G.; Paraskeva, E.; Simos, G. Casein kinase 1 regulates human hypoxia-inducible factor HIF-1. J. Cell Sci. 2010,123, 2976-2986. [CrossRef]
  • 135. Kourti, M.; Ikonomou, G.; Giakoumakis, N.-N.; Rapsomaniki, M.A.; Landegren, U.; Siniossoglou, S.; Lygerou, Z.; Simos, G.; Mylonis, I. CK1delta restrains lipin-1 induction, lipid droplet formation and cell proliferation under hypoxia by reducing HIF-1a/ARNT complex formation. Cell. Signal. 2015, 27,1129-1140. [CrossRef] [PubMed]
  • 136. Gkotinakou, I.-M.; Befani, C.; Simos, G.; Liakos, P. ERK1/2 phosphorylates HIF-2a and regulates its activity by controlling its CRM1-dependent nuclear shuttling. J. Cell Sci. 2019,132, jcs225698. [CrossRef]
  • 137. Koukoulas, K.; Giakountis, A.; Karagiota, A.; Samiotaki, M.; Panayotou, G.; Simos, G.; Mylonis, I. ERK signaling controls productive HIF-1 binding to chromatin and cancer cell adaptation to hypoxia through HIF-1a interaction with NPM1. Mol. Oncol. 2021,15, 3468-3489. [CrossRef]
  • 138. Mylonis, I.; Chachami, G.; Samiotaki, M.; Panayotou, G.; Paraskeva, E.; Kalousi, A.; Georgatsou, E.; Bonanou, S.; Simos, G. Identification of MAPK Phosphorylation Sites and Their Role in the Localization and Activity of hypoxia-inducible Factor-1 a. J. Biol. Chem. 2006, 281, 33095-33106. [CrossRef]
  • 139. Mylonis, I.; Chachami, G.; Paraskeva, E.; Simos, G. Atypical CRM1-dependent Nuclear Export Signal Mediates Regulation of hypoxia-inducible Factor-1 a by MAPK. J. Biol. Chem. 2008, 283,27620-27627. [CrossRef]
  • 140. Gkotinakou, I.M.; Befani, C.; Samiotaki, M.; Panayotou, G.; Liakos, P. Novel HIF-2a interaction with Reptin52 impairs HIF-2 transcriptional activity and EPO secretion. Biochem. Biophys. Res. Commun. 2021, 557,143-150. [CrossRef]
  • 141. Zhang, A.; Huang, Z.; Tao, W.; Zhai, K.; Wu, Q.; Rich, J.N.; Zhou, W.; Bao, S. USP33 deubiquitinates and stabilizes HIF-2alpha to promote hypoxia response in glioma stem cells. EMBO J. 2022, 41, e109187. [CrossRef]
  • 142. Cordes, T.; Diesing, D.; Becker, S.; Diedrich, K.; Reichrath, J.; Friedrich, M. Modulation of MAPK ERK1 and ERK2 in VDR-positive and -negative Breast Cancer Cell Lines. Anticancer Res. 2006, 26, 2749-2754.
  • 143. Semenza, G.L. Heritable disorders of oxygen sensing. Am. J. Med Genet. Part A 2021,185, 2576-2581. [CrossRef]
  • 144. Keith, B.; Johnson, R.S.; Simon, M.C. HIF1a and HIF2a: Sibling rivalry in hypoxic tumour growth and progression. Nat. Rev. Cancer 2011,12, 9-22. [CrossRef]
  • 145. Semenza, G.L. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2009, 29, 625-634. [CrossRef]
  • 146. Semenza, G.L. Pharmacologic Targeting of hypoxia-Inducible Factors. Annu. Rev. Pharmacol. Toxicol. 2019,59,379-403. [CrossRef]
  • 147. Huang, C.-Y.; Weng, Y.-T.; Li, P.-C.; Hsieh, N.-T.; Li, C.-I.; Liu, H.-S.; Lee, M.-F. Calcitriol Suppresses Warburg Effect and Cell Growth in Human Colorectal Cancer Cells. Life 2021,11, 963. [CrossRef]
  • 148. Pálmer, H.G.; González-Sancho, J.M.; Espada, J.; Berciano, M.T.; Puig, I.; Baulida, J.; Quintanilla, M.; Cano, A.; de Herreros, A.G.; Lafarga, M.; et al. Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J. Cell Biol. 2001,154, 369-387. [CrossRef]
  • 149. Shah, S.; Islam, N.; Dakshanamurthy, S.; Rizvi, I.; Rao, M.; Herrell, R.; Zinser, G.; Valrance, M.; Aranda, A.; Moras, D.; et al. The Molecular Basis of Vitamin D Receptor and |3-Catenin Crossregulation. Mol. Cell 2006, 21, 799-809. [CrossRef]
  • 150. Xu, H.; Posner, G.H.; Stevenson, M.; Campbell, F.C. Apc MIN modulation of vitamin D secosteroid growth control. Carcinogenesis 2010, 31,1434-1441. [CrossRef]
  • 151. Aguilera, O.; Peña, C.; García, J.M.; Jesús Larriba, M.; Ordóñez-Morán, P.; Navarro, D.; Barbáchano, A.; López de Silanes, I.; Ballestar, E.; Fraga, M.F.; et al. The Wnt antagonist DICKKOPF-1 gene is induced by 1,25-dihydroxyvitamin D3 associated to the differentiation of human colon cancer cells. Carcinogenesis 2007,28,1877-1884. [CrossRef]
  • 152. Pendás-Franco, N.; García, J.M.; Peña, C.; Valle, N.; Pálmer, H.G.; Heinaniemi, M.; Carlberg, C.; Jiménez, B.; Bonilla, F.; Muñoz, A.; et al. DICKKOPF-4 is induced by TCF/beta-catenin and upregulated in human colon cancer, promotes tumour cell invasion and angiogenesis and is repressed by 1alpha,25-dihydroxyvitamin D3. Oncogene 2008, 27, 4467-4477. [CrossRef]
  • 153. Cordero, J.B.; Cozzolino, M.; Lu, Y.; Vidal, M.; Slatopolsky, E.; Stahl, P.D.; Barbieri, M.A.; Dusso, A. 1,25-Dihydroxyvitamin D Down-regulates Cell Membrane Growth- and Nuclear Growth-promoting Signals by the Epidermal Growth Factor Receptor . J. Biol. Chem. 2002, 277,38965-38971. [CrossRef]
  • 154. McGaffin, K.R.; Chrysogelos, S.A. Identification and characterization of a response element in the EGFR promoter that mediates transcriptional repression by 1,25-dihydroxyvitamin D3 in breast cancer cells. J. Mol. Endocrinol. 2005, 35,117-133. [CrossRef]
  • 155. Tong, W.M.; Hofer, H.; Ellinger, A.; Peterlik, M.; Cross, H.S. Mechanism of antimitogenic action of vitamin D in human colon carcinoma cells: Relevance for suppression of epidermal growth factor-stimulated cell growth. Oncol. Res. Featur. Preclin. Clin. Cancer Ther. 1999,11, 77-84.
  • 156. Colston, K.W.; Perks, C.M.; Xie, S.P.; Holly, J.M. Growth inhibition of both MCF-7 and Hs578T human breast cancer cell lines by vitamin D analogues is associated with increased expression of insulin-like growth factor binding protein-3. J. Mol. Endocrinol. 1998, 20,157-162. [CrossRef]
  • 157. Sprenger, C.C.; Peterson, A.; Lance, R.; Ware, J.L.; Drivdahl, R.H.; Plymate, S.R. Regulation of proliferation of prostate epithelial cells by 1,25-dihydroxyvitamin D3 is accompanied by an increase in insulin-like growth factor binding protein-3. J. Endocrinol. 2001,170, 609-618. [CrossRef]
  • 158. Yang, E.S.; Burnstein, K.L. Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm. J. Biol. Chem. 2003, 278, 46862-46868. [CrossRef]
  • 159. Blutt, S.E.; McDonnell, T.J.; Polek, T.C.; Weigel, N.L. Calcitriol-induced apoptosis in LNCaP cells is blocked by overex-pression of Bcl-2. Endocrinology 2000,141,10-17. [CrossRef]
  • 160. Wagner, N.; Wagner, K.-D.; Schley, G.; Badiali, L.; Theres, H.; Scholz, H. 1,25-dihydroxyvitamin D3-induced apoptosis of retinoblastoma cells is associated with reciprocal changes of Bcl-2 and bax. Exp. Eye Res. 2003, 77,1-9. [CrossRef]
  • 161. Reitsma, P.H.; Rothberg, P.G.; Astrin, S.M.; Trial, J.; Bar-Shavit, Z.; Hall, A.; Teitelbaum, S.; Kahn, A.J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature 1983, 306, 492-494. [CrossRef] [PubMed]
  • 162. Rohan, J.N.P.; Weigel, N.L. 1 a,25-Dihydroxyvitamin D3 Reduces c-Myc Expression, Inhibiting Proliferation and Causing G1 Accumulation in C4-2 Prostate Cancer Cells. Endocrinology 2009,150, 2046-2054. [CrossRef] [PubMed]
  • 163. Moreno, J.; Krishnan, A.V.; Swami, S.; Nonn, L.; Peehl, D.M.; Feldman, D. Regulation of Prostaglandin Metabolism by Calcitriol Attenuates Growth Stimulation in Prostate Cancer Cells. Cancer Res. 2005, 65, 7917-7925. [CrossRef] [PubMed]
  • 164. Nonn, L.; Peng, L.; Feldman, D.; Peehl, D.M. Inhibition of p38 by Vitamin D Reduces Interleukin-6 Production in Normal Prostate Cells via Mitogen-Activated Protein Kinase Phosphatase 5: Implications for Prostate Cancer Prevention by Vitamin D. Cancer Res. 2006, 66, 4516-4524. [CrossRef] [PubMed]
  • 165. Harant, H.; Wolff, B.; Lindley, I.J. 1Alpha,25-dihydroxyvitamin D3 decreases DNA binding of nuclear factor-kappaB in human fibroblasts. FEBS Lett. 1998, 436, 329-334. [CrossRef]
  • 166. Iseki, K.; Tatsuta, M.; Uehara, H.; Iishi, H.; Yano, H.; Sakai, N.; Ishiguro, S. Inhibition of angiogenesis as a mechanism for inhibition by 1-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 of colon carcinogenesis induced by azoxymethane in wistar rats. Int. J. Cancer 1999, 81, 730-733. [CrossRef]
  • 167. Merrigan, S.L.; Park, B.; Ali, Z.; Jensen, L.D.; Corson, T.W.; Kennedy, B.N. Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis ex vivo and in vivo. Oncotarget 2020, 11, 493-509. [CrossRef]
  • 168. Calvani, M.; Trisciuoglio, D.; Bergamaschi, C.; Shoemaker, R.H.; Melillo, G. Differential Involvement of Vascular Endothelial Growth Factor in the Survival of Hypoxic Colon Cancer Cells. Cancer Res. 2008, 68, 285-291. [CrossRef]
  • 169. Górlach, A.; Diebold, I.; Schini-Kerth, V.B.; Berchner-Pfannschmidt, U.; Roth, U.; Brandes, R.P.; Kietzmann, T.; Busse, R. Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: Role of the p22(phox)-containing NADPH oxidase. Circ. Res. 2001, 89, 47-54. [CrossRef]
  • 170. Kietzmann, T.; Mennerich, D.; Dimova, E.Y. hypoxia-Inducible Factors (HIFs) and Phosphorylation: Impact on Stability, Localization, and Transactivity. Front. Cell Dev. Biol. 2016, 4,11. [CrossRef]
  • 171. Richard, D.E.; Berra, E.; Pouysségur, J. Nonhypoxic Pathway Mediates the Induction of hypoxia-inducible Factor 1a in Vascular Smooth Muscle Cells. J. Biol. Chem. 2000, 275, 26765-26771. [CrossRef]
  • 172. Stiehl, D.; Jelkmann, W.; Wenger, R.H.; Hellwig-Bürgel, T. Normoxic induction of the hypoxia-inducible factor 1a by insulin and interleukin-113 involves the phosphatidylinositol 3-kinase pathway. FEBS Lett. 2002, 512,157-162. [CrossRef]
  • 173. Liu, Q.; Liu, L.; Zhao, Y.; Zhang, J.; Wang, D.; Chen, J.; He, Y.; Wu, J.; Zhang, Z.; Liu, Z. hypoxia Induces Genomic DNA Demethylation through the Activation of HIF-1a and Transcriptional Upregulation of MAT2A in Hepatoma Cells. Mol. Cancer Ther. 2011,10,1113-1123. [CrossRef]
  • 174. Minet, E.; Arnould, T.; Michel, G.; Roland, I.; Mottet, D.; Raes, M.; Remacle, J.; Michiels, C. ERK activation upon hypoxia: Involvement in HIF-1 activation. FEBS Lett. 2000, 468, 53-58. [CrossRef]
  • 175. Krishnan, A.V.; Feldman, D. Mechanisms of the Anti-Cancer and Anti-Inflammatory Actions of Vitamin D. Annu. Rev. Pharmacol. Toxicol. 2011, 51, 311-336. [CrossRef]
  • 176. Schneikert, J.; Behrens, J. The canonical Wnt signalling pathway and its APC partner in colon cancer development. Gut 2007,56, 417-425. [CrossRef]
  • 177. Barbáchano, A.; Ordóñez-Morán, P.; García, J.M.; Sánchez, A.; Pereira, F.; Larriba, M.J.; Martínez, N.; Hernández, J.; Landolfi, S.; Bonilla, F.; et al. SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity. Oncogene 2010, 29, 4800-4813. [CrossRef]
  • 178. Cui, M.; Zhao, Y.; Hance, K.W.; Shao, A.; Wood, R.J.; Fleet, J.C. Effects of MAPK signaling on 1,25-dihydroxyvitamin D-mediated CYP24 gene expression in the enterocyte-like cell line, Caco-2. J. Cell. Physiol. 2009, 219,132-142. [CrossRef]
  • 179. Zhang, Z.; Kovalenko, P.; Cui, M.; DeSmet, M.; Clinton, S.K.; Fleet, J.C. Constitutive activation of the mitogen-activated protein kinase pathway impairs vitamin D signaling in human prostate epithelial cells. J. Cell. Physiol. 2010,224, 433-442. [CrossRef]
  • 180. Peng, L.; Malloy, P.J.; Feldman, D. Identification of a Functional Vitamin D Response Element in the Human Insulin-Like Growth Factor Binding Protein-3 Promoter. Mol. Endocrinol. 2004,18,1109-1119. [CrossRef]
  • 181. Boyle, B.J.; Zhao, X.Y.; Cohen, P.; Feldman, D. Insulin-like growth factor binding protein-3 mediates 1 al-pha,25-dihydroxyvitamin d(3) growth inhibition in the LNCaP prostate cancer cell line through p21/WAF1. J. Urol. 2001,165,1319-1324. [CrossRef]
  • 182. Blutt, S.E.; Allegretto, E.A.; Pike, J.W.; Weigel, N.L. 1,25-Dihydroxyvitamin D3 and 9-cis-Retinoic Acid Act Synergistically to Inhibit the Growth of LNCaP Prostate Cells and Cause Accumulation of Cells in G1*. Endocrinology 1997, 138, 1491-1497. [CrossRef]
  • 183. Liu, M.; Lee, M.H.; Cohen, M.; Bommakanti, M.; Freedman, L.P. Transcriptional activation of the Cdk inhibitor p21 by vitamin D3 leads to the induced differentiation of the myelomonocytic cell line U937. Genes Dev. 1996,10,142-153. [CrossRef]
  • 184. Lin, R.; Nagai, Y.; Sladek, R.; Bastien, Y.; Ho, J.; Petrecca, K.; Sotiropoulou, G.; Diamandis, E.P.; Hudson, T.J.; White, J.H. Expression profiling in squamous carcinoma cells reveals pleiotropic effects of vitamin D3 analog EB1089 signaling on cell proliferation, differentiation, and immune system regulation. Mol. Endocrinol. 2002,16,1243-1256. [CrossRef]
  • 185. Lin, R.; White, J.H. The pleiotropic actions of vitamin D. BioEssays 2004,26, 21-28. [CrossRef]
  • 186. Brahimi-Horn, M.C.; Ben-Hail, D.; Ilie, M.; Gounon, P.; Rouleau, M.; Hofman, V.; Doyen, J.; Mari, B.; Shoshan-Barmatz, V.; Hofman, P.; et al. Expression of a Truncated Active Form of VDAC1 in Lung Cancer Associates with Hypoxic Cell Survival and Correlates with Progression to Chemotherapy Resistance. Cancer Res. 2012, 72, 2140-2150. [CrossRef]
  • 187. Brahimi-Horn, M.C.; Giuliano, S.; Saland, E.; Lacas-Gervais, S.; Sheiko, T.; Pelletier, J.; Bourget, I.; Bost, F.; Feral, C.; Boulter, E.; et al. Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation. Cancer Metab. 2015, 3, 8. [CrossRef]
  • 188. Mylonis, I.; Kourti, M.; Samiotaki, M.; Panayotou, G.; Simos, G. Mortalin-mediated and ERK-controlled targeting of HIF-1 a to mitochondria confers resistance to apoptosis under hypoxia. J. Cell Sci. 2017,130, 466-479. [CrossRef]
  • 189. Allavena, P.; Garlanda, C.; Borrello, M.G.; Sica, A.; Mantovani, A. Pathways connecting inflammation and cancer. Curr. Opin. Genet. Dev. 2008,18, 3-10. [CrossRef]
  • 190. Lucia, M.S.; Torkko, K.C. Inflammation as a target for prostate cancer chemoprevention: Pathological and laboratory rationale. J. Urol. 2004,171, S30-S34.
  • 191. Eltzschig, H.K.; Bratton, D.L.; Colgan, S.P. Targeting hypoxia signalling for the treatment of ischaemic and inflammatory diseases. Nat. Rev. Drug Discov. 2014,13, 852-869. [CrossRef] [PubMed]
  • 192. Folkman, J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat. Med. 1995,1, 27-31. [CrossRef] [PubMed]
  • 193. Rosmorduc, O.; Housset, C. hypoxia: A Link between Fibrogenesis, Angiogenesis, and Carcinogenesis in Liver Disease. Semin. Liver Dis. 2010, 30, 258-270. [CrossRef] [PubMed]
  • 194. Hassan, M.; Selimovic, D.; Ghozlan, H.; Abdel-Kader, O. Hepatitis C virus core protein triggers hepatic angiogenesis by a mechanism including multiple pathways. Hepatology 2009, 49,1469-1482. [CrossRef] [PubMed]
  • 195. Giaccia, A.; Siim, B.G.; Johnson, R. HIF-1 as a target for drug development. Nat. Rev. Drug Discov. 2003,2, 803-811. [CrossRef]
  • 196. Rankin, E.B.; Giaccia, A.J. The role of hypoxia-inducible factors in tumorigenesis. Cell Death Differ. 2008,15, 678-685. [CrossRef] [PubMed]
  • 197. Von Marschall, Z.; Cramer, T.; Hocker, M.; Finkenzeller, G.; Wiedenmann, B.; Rosewicz, S. Dual mechanism of vascular endothelial growth factor upregulation by hypoxia in human hepatocellular carcinoma. Gut 2001, 48, 87-96. [CrossRef]
  • 198. Bougatef, F.; Quemener, C.; Kellouche, S.; Naïmi, B.; Podgorniak, M.-P.; Millot, G.; Gabison, E.E.; Calvo, F.; Dosquet, C.; Lebbé, C.; et al. EMMPRIN promotes angiogenesis through hypoxia-inducible factor-2a-mediated regulation of soluble VEGF isoforms and their Receptor VEGFR-2. Blood 2009,114, 5547-5556. [CrossRef]
  • 199. Imura, S.; Miyake, H.; Izumi, K.; Tashiro, S.; Uehara, H. Correlation of vascular endothelial cell proliferation with microvessel density and expression of vascular endothelial growth factor and basic fibroblast growth factor in hepatocellular carcinoma. J. Med. Investig. 2004, 51, 202-209. [CrossRef]
  • 200. Simiantonaki, N.; Jayasinghe, C.; Michel-Schmidt, R.; Peters, K.; Hermanns, M.I.; Kirkpatrick, C.J. hypoxia-induced epi-thelial VEGF-C/VEGFR-3 upregulation in carcinoma cell lines. Int. J. Oncol. 2008, 32, 585-592.
  • 201. Chiang, K.-C.; Chen, T.C. The anti-cancer actions of vitamin D. Anti Cancer Agents Med. Chem. 2013,13,126-139. [CrossRef]
  • 202. Ben-Shoshan, M.; Amir, S.; Dang, D.T.; Dang, L.H.; Weisman, Y.; Mabjeesh, N.J. 1 a,25-dihydroxyvitamin D3 (Calcitriol) inhibits hypoxia-inducible factor-1/vascular endothelial growth factor pathway in human cancer cells. Mol. Cancer Ther. 2007, 6, 1433-1439. [CrossRef]
  • 203. Whitfield, G.K.; Lenore, S.R.; Peter, W.J.; Heike, Z.; Anish, K.O.; Hope, T.L.D.; Carol, A.H.; Michael, A.G.; Michelle, L.T.; Carlos Encinas, D.; et al. Functionally relevant polymorphisms in the human nuclear vitamin D Receptor gene. Mol. Cell. Endocrinol. 2001,177,145-159. [CrossRef]
  • 204. Uitterlinden, A.G.; Fang, Y.; van Meurs, J.B.; Pols, H.A.; van Leeuwen, J.P. Genetics and biology of vitamin D Receptor polymorphisms. Gene 2004, 338,143-156. [CrossRef]
  • 205. Raimondi, S.; Johansson, H.; Maisonneuve, P.; Gandini, S. Review and meta-analysis on vitamin D Receptor polymorphisms and cancer risk. Carcinogenesis 2009, 30,1170-1180. [CrossRef]
  • 206. Ben-Eltriki, M.; Deb, S.; Guns, E.S.T. Calcitriol in Combination Therapy for Prostate Cancer: Pharmacokinetic and Pharmacodynamic Interactions. J. Cancer 2016, 7, 391-407. [CrossRef]
  • 207. Hu, K.; Callen, D.F.; Li, J.; Zheng, H. Circulating Vitamin D and Overall Survival in Breast Cancer Patients: A Dose-Response Meta-Analysis of Cohort Studies. Integr. Cancer Ther. 2018,17, 217-225. [CrossRef]
  • 208. Trump, D.L. Calcitriol and cancer therapy: A missed opportunity. Bone Rep. 2018, 9,110-119. [CrossRef]
  • 209. Cabrera-Cano, A.; Dávila-Borja, V.M.; Juárez-Méndez, S.; Marcial-Quino, J.; Gómez-Manzo, S.; Castillo-Rodríguez, R.A. hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia. Cell Biochem. Funct. 2021, 39, 478-487. [CrossRef]
  • 210. Zhalehjoo, N.; Shakiba, Y.; Panjehpour, M. Gene expression profiles of CYP24A1 and CYP27B1 in malignant and normal breast tissues. Mol. Med. Rep. 2016,15, 467-473. [CrossRef]
  • 211. Ma, R.; Gu, Y.; Zhao, S.; Sun, J.; Groome, L.J.; Wang, Y. Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am. J. Physiol. Metab. 2012, 303, E928-E935. [CrossRef]
  • 212. Beer, T.M.; Myrthue, A. Calcitriol in the treatment of prostate cancer. Anticancer Res. 2006, 26, 2647-2652.
  • 213. Osborn, J.L.; Schwartz, G.G.; Smith, D.C.; Bahnson, R.; Day, R.; Trump, D.L. Phase II trial of oral 1,25-dihydroxyvitamin D (calcitriol) in hormone refractory prostate cancer. Urol. Oncol. Semin. Orig. Investig. 1995,1,195-198. [CrossRef]
  • 214. Beer, T.M.; Garzotto, M.; Katovic, N.M. High-Dose Calcitriol and Carboplatin in Metastatic Androgen-Independent Prostate Cancer. Am. J. Clin. Oncol. 2004, 27, 535-541. [CrossRef]
  • 215. Beer, T.M.; Eilers, K.M.; Garzotto, M.; Egorin, M.J.; Lowe, B.A.; Henner, W.D. Weekly High-Dose Calcitriol and Docetaxel in Metastatic Androgen-Independent Prostate Cancer. J. Clin. Oncol. 2003, 21,123-128. [CrossRef]
  • 216. Trump, D.L.; Potter, D.M.; Muindi, J.; Brufsky, A.; Johnson, C.S. Phase II trial of high-dose, intermittent calcitriol (1,25 dihydrox-yvitamin D3) and dexamethasone in androgen-independent prostate cancer. Cancer 2006,106, 2136-2142. [CrossRef]
  • 217. Guan, X.; Ding, Y.; Qi, T. Safety and efficacy of high dose pulse calcitriol and docetaxel for androgen-independent prostate cancer. Med. Case Rep. Study Protoc. 2021,2, e0151. [CrossRef]
  • 218. Sanghani, N.S.; Haase, V.H. hypoxia-Inducible Factor Activators in Renal Anemia: Current Clinical Experience. Adv. Chronic Kidney Dis. 2019, 26, 253-266. [CrossRef]
  • 219. Chen, W.; Hill, H.; Christie, A.; Kim, M.S.; Holloman, E.; Pavia-Jimenez, A.; Homayoun, F.; Ma, Y.; Patel, N.; Yell, P.; et al. Targeting renal cell carcinoma with a HIF-2 antagonist. Nature 2016, 539,112-117. [CrossRef]
  • 220. Cho, H.; Du, X.; Rizzi, J.P.; Liberzon, E.; Chakraborty, A.A.; Gao, W.; Carvo, I.; Signoretti, S.; Bruick, R.K.; Josey, J.A.; et al. On-target efficacy of a HIF-2a antagonist in preclinical kidney cancer models. Nature 2016, 539,107-111. [CrossRef]
  • 221. Courtney, K.D.; Infante, J.R.; Lam, E.T.; Figlin, R.A.; Rini, B.I.; Brugarolas, J.; Zojwalla, N.J.; Lowe, A.M.; Wang, K.; Wallace, E.M.; et al. Phase I Dose-Escalation Trial of PT2385, a First-in-Class hypoxia-Inducible Factor-2a Antagonist in Patients with Previously Treated Advanced Clear Cell Renal Cell Carcinoma. J. Clin. Oncol. 2018, 36, 867-874. [CrossRef] [PubMed]
  • 222. Wu, J.; Yang, N.; Yuan, M. Dietary and circulating vitamin D and risk of renal cell carcinoma: A meta-analysis of observational studies. Int. Braz. J. Urol 2021, 47, 733-744. [CrossRef] [PubMed]
  • 223. Mylonis, I.; Lakka, A.; Tsakalof, A.; Simos, G. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions. Biochem. Biophys. Res. Commun. 2010, 398, 74-78. [CrossRef] [PubMed]
  • 224. Lim, H.Y.; Ong, P.S.; Wang, L.; Goel, A.; Ding, L.; Wong, A.L.-A.; Ho, P.C.-L.; Sethi, G.; Xiang, X.; Goh, B.C. Celastrol in cancer therapy: Recent developments, challenges and prospects. Cancer Letters 2021, 521, 252-267. [CrossRef] [PubMed]
  • 225. Ren, B.; Kwah, M.X.-Y.; Liu, C.; Ma, Z.; Shanmugam, M.K.; Ding, L.; Xiang, X.; Ho, P.C.-L.; Wang, L.; Ong, P.S.; et al. Resveratrol for cancer therapy: Challenges and future perspectives. Cancer Letters 2021, 515, 63-72. [CrossRef] [PubMed]


Google Scholar Search (hypoxia cancer "vitamin d") 5,600 items as of April 2022

Google Scholar Query Examples

  • Hypoxia and cancer Nov 2007PDF
  • Hypoxia as a modulator of cytochromes P450: Overexpression of the cytochromes CYP2S1 and CYP24A1 in human liver cancer cells in hypoxia - July 2021 https://doi.org/10.1002/cbf.3612
  • Preclinical Researches of Vitamin D Role in Preventing Malignant Diseased, a Systematic Review 2021 PDF
  • Molecular Link between Vitamin D and Cancer Prevention - Sept 2013
  • Role of hypoxia in cancer therapy by regulating the tumor microenvironment - Nov 2019 PDF
  • The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy - 2015 PDF
  • Tumor Hypoxia as a Barrier in Cancer Therapy: Why Levels Matter - 2021 PDF
  • High altitude and cancer: An old controversy - July 2021 https://doi.org/10.1016/j.resp.2021.103655
    • "Cancer prevalence and mortality is lower in high altitude populations of the United States and China, but higher in high altitude dwellers of Ecuador and India./// Some genetic and molecular modifications that allow for chronic hypoxia tolerance are known to facilitate oncogenesis.// /Lung cancer, lymphoma, colon cancer, esophageal carcinoma may have a decreased incidence at high altitude/// Gallbladder and biliary duct cancer, stomach carcinoma, skin cancer may be more frequent at high altitude."

Vitamin D Life - Cancer category starts


Cancers get less Vitamin D when there is a poor Vitamin D Receptor


Vitamin D Life Vitamin D Receptor pages with CANCER in title (75 as of April 2022)

This list is automatically updated

Items found: 86
Title Modified
Vitamin D Receptor (Cancers OR Viruses) - many studies 02 Mar, 2024
Oral Cancer and Vitamin D and VDR - several studies 11 Feb, 2024
Breast Cancer risk reduced if consume butyrate - Dec 2023 23 Jan, 2024
An activated Vitamin D Receptor fights Autoimmune Diseases, Infections, Cancers, etc. – Dec 2023 13 Jan, 2024
Cervical Cancer is prevented by Vitamin D, and treated if caught early (genes are important) – May 2023 27 May, 2023
Colon Cancer protects itself by changing the VDR and CYP3A4 genes – Dec 2022 06 Dec, 2022
Breast cancer spreads to bone if poor vitamin D Receptor (no surprise) – Oct 2022 31 Oct, 2022
2X more Thyroid Cancer malignancy if less than 15 ng of vitamin D – June 2012 16 Sep, 2022
Cancers are associated with low vitamin D, poor vaccination response and perhaps poor VDR – July 2022 15 Aug, 2022
Poor prognosis of solid childhood cancers 14.7 X more likely with a poor Vitamin D Receptor – July 2022 27 Jul, 2022
Breast Cancer, Vitamin D, and genes – Welsh Nov 2021 09 Feb, 2022
How cancer is fought by Vitamin D (Ovarian this time) - Feb 2020 01 Nov, 2021
Lung Cancer is up to 7 X more deadly if poor vitamin D genes – Oct 2021 25 Oct, 2021
Cancers and Vitamin D Receptors, including change with race – Feb 2021 24 Oct, 2021
Breast Cancer reduces receptor and thus blocks Vitamin D to the cells – several studies 18 Oct, 2021
After lactation Vitamin D levels are low, increased risk of Breast Cancer, vitamin D should decrease risk – Aug 2021 20 Aug, 2021
Breasts process Vitamin D and change gene activation, might prevent breast cancer if given more Vit. D – July 2021 10 Jul, 2021
Oral Cancers - increased risk if low vitamin D or poor vitamin D genes 22 Jan, 2021
Colon cancer risk increases 30X if you have the worst vitamin D receptor mutation – Jan 2021 15 Jan, 2021
Book: Sunlight, UV, Vitamin D and Receptor, Skin and other Cancers - Dec 2020 09 Dec, 2020
Colorectal Cancer Patients 2.4 X more likely to have poor Vitamin D receptors (less D to cells) – April 2020 02 May, 2020
Colorectal cancer linked to poor Vitamin D Receptor (yet again) – Jan 2020 22 Jan, 2020
8 ways that Cancer might be prevented by Vitamin D - June 2019 26 Dec, 2019
Liver Cancer – higher risk if poor genes (Vitamin D receptor etc) – meta-analysis Dec 2019 14 Dec, 2019
Prostate Cancer associated with various genes, including Vitamin D Receptor and CYP24A1 – Nov 2019 15 Nov, 2019
Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016 09 Nov, 2019
Cancer is leading cause of death - Vitamin D and Receptor activators help 09 Nov, 2019
Melanoma cancer growth slowed by increased Vitamin D Receptor (yet again) – Oct 2019 06 Nov, 2019
Breast cancer associated with Vitamin D Receptor (14th study) – Oct 2019 19 Oct, 2019
Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019 23 Aug, 2019
Breast Cancer death 1.8 X more likely if poor Vitamin D Receptor – April 2019 29 Jul, 2019
Multiple Myeloma (blood cell cancer) treated by vitamin D - many studies 14 Jun, 2019
Blood cell cancer is associated with a 3X worse Vitamin D Receptor – June 2019 14 Jun, 2019
Lung Cancer more likely if poor Vitamin D Receptor – meta-analysis June 2019 13 Jun, 2019
After breast cancer treatment 4,000 IU of Vitamin D was not enough to help if have poor Vitamin D receptor – June 2019 04 Jun, 2019
Effects of Resveratrol against Lung Cancer in mice – Nov 2017 28 Apr, 2019
The Role of Resveratrol in Cancer Therapy – Dec 2017 27 Apr, 2019
Good Vitamin D receptor reduced bladder cancer and cisplatin deaths – April 2019 11 Apr, 2019
A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019 26 Mar, 2019
Breast Cancer and Vitamin D review – March 2018 17 Mar, 2019
Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018 15 Mar, 2019
Women with Breast Cancer were 16.9 times more likely to have a poor Vitamin D Receptor – Jan 2019 11 Feb, 2019
Risks of Colorectal Cancer, IBD, etc slightly increased if poor Vitamin D Receptor – Aug 2018 09 Dec, 2018
Ovarian Cancer risk reduced if higher vitamin D, more UVB, or better vitamin D receptor – Nov 2018 10 Nov, 2018
Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018 01 Nov, 2018
Brain cancer in 175 countries related to low UVB and low vitamin D – Oct 2010 03 Oct, 2018
Pancreatic Cancer – live a year longer if have high vitamin D and good Vitamin D Receptor – Aug 2018 15 Aug, 2018
Endometriosis, Endometrial Cancer, and poor Vitamin D or Receptor – Aug 2018 08 Aug, 2018
Risk of colon cancer increases in mice with no Vitamin D receptor in colon - July 2018 07 Jul, 2018
Vitamin D receptor is essential for both normal and cancerous cells in the lab – June 2018 16 Jun, 2018
Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018 28 Mar, 2018
Two chemicals increase the Vitamin D receptor and decrease the growth of breast cancer cells in the lab - March 2018 17 Mar, 2018
Ovarian Cancer in Asia is 1.5 X more likely if poor Vitamin D receptor – meta-analysis Dec 2017 14 Dec, 2017
Nonmelanoma Skin Cancer 2X more likely if poor Vitamin D Receptor – Oct 2017 19 Oct, 2017
Cancer and the Vitamin D Receptor, a primer – Sept 2017 01 Oct, 2017
Thyroid Cancer rate has increased 3X in 3 decades, Vitamin D Receptor decreases, Calcium increases – Aug 2017 26 Aug, 2017
Advanced Colon Cancer risk is doubled or halved with 1000 IU of Vitamin D, depends on Vitamin D Receptors – RCT May 2017 19 Aug, 2017
Cancer risks and Vitamin D Receptors – association is unclear – 2017 19 Aug, 2017
Increased Breast Cancer metastasis if low vitamin D or poor VDR – Feb 2016 09 Aug, 2017
Colon Cancer survival 3.1 X less likely if poor Vitamin D Receptor – Aug 2017 02 Aug, 2017
Lung Cancer patients were 2.4 times more likely to have a poor Vitamin D Receptor gene – July 2017 27 Jul, 2017
Pancreatic Cancer massively deregulates the local Vitamin D receptors and CPY24A1 – July 2014 25 Jul, 2017
Gastric Cancer 2.7 X more likely if poor Vitamin D Receptor (Chinese) – 2015 15 Jun, 2017
Skin Cancers, Vitamin D, Vitamin D Receptor and Genes – Jan 2015 17 Mar, 2017
Prostate cancer in black men is 1.6 times more likely if a poor Vitamin D Receptor – Feb 2017 06 Mar, 2017
2X more likely to survive a form of esophageal cancer in China if have good vitamin D receptor – Feb 2017 04 Mar, 2017
Urinary Bladder Cancer survival is associated with vitamin D receptor: 14 months vs 53 months – Oct 2015 02 Mar, 2017
Vitamin D receptor as a target for breast cancer therapy (abstract only) – Feb 2017 01 Mar, 2017
Ovarian Cancer 5.8 X more likely if both low vitamin D and Fok1 gene change – May 2013 27 Feb, 2017
Vitamin D receptor may suppress skin cancer – Dec 2013 27 Jan, 2017
Aggressive Prostate Cancer in blacks with low vitamin D – 7X more likely if added Calcium – Jan 2017 28 Dec, 2016
Breast Cancer was 4.6 times more likely if have a poor Vitamin D Receptor – Dec 2016 06 Dec, 2016
Vitamin D, Vitamin D Receptor and Cancer – Nov 2016 05 Dec, 2016
High PSA readings with Prostate Cancer 4 times more likely if poor Vitamin D receptor – March 2016 14 Nov, 2016
2X less prostate cancer in A-A with low Calcium is due vitamin D receptor gene – July 2013 14 Nov, 2016
Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014 12 Nov, 2016
10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012 23 Sep, 2016
Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013 17 Mar, 2016
Skin cancer 20 percent more likely with some Vitamin D receptor gene polymorphisms – Oct 2015 06 Jan, 2016
Pancreatic Cancer treatment by calcipotriol (a synthetic vitamin D) improves outcome by 57 percent – Sept 2014 13 Dec, 2015
Poor Bladder Cancer survival associated with poor Vitamin D receptor – Oct 2015 18 Oct, 2015
Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015 03 May, 2015
Free vitamin D (VDR) may be more important than total for bladder cancer – March 2013 06 Jan, 2014
Genes breast cancer and vitamin D receptor - Sept 2010 08 Jul, 2013
Breast Cancer incidence change by 40 percent with vitamin D receptor genes – Oct 2012 08 Jul, 2013
Vitamin D receptor in breasts and breast cancer vary with race – March 2013 08 Jul, 2013

Created by admin. Last Modification: Wednesday April 13, 2022 15:51:19 GMT-0000 by admin. (Version 16)

Attached files

ID Name Comment Uploaded Size Downloads
17406 The role of hypoxia in cancer progression.pdf admin 13 Apr, 2022 686.36 Kb 145
17405 Tumor Hypoxia as a Barrier Jan 2021_CompressPdf.pdf admin 13 Apr, 2022 415.68 Kb 105
17403 Role of hypoxia in cancer therapy.pdf admin 13 Apr, 2022 1,006.18 Kb 484
17402 Preclinical Researches of Vitamin D Role.pdf admin 13 Apr, 2022 520.22 Kb 110
17401 Hypoxia and cancer.pdf admin 13 Apr, 2022 320.11 Kb 103
17400 Vitamin D, Hypoxia, Cancer_CompressPdf.pdf admin 13 Apr, 2022 462.33 Kb 123
17399 Cancer Hypoxia.jpg admin 13 Apr, 2022 54.52 Kb 303