Vitamin D-VDR signaling inhibits Wnt/beta-catenin-mediated melanoma progression and promotes anti-tumor immunity
Cancer Research DOI: 10.1158/0008-5472.CAN-18-3927
The risk of 44 diseases at least double with poor Vitamin D Receptor as of Oct 2019
Vitamin D Receptor Activation can be increased by any of:
Resveratrol, Omega-3, Magnesium, Zinc, non-daily Vitamin D dosing, etc
Note: The founder of Vitamin D Life uses 10 of the 12 known VDR activators
I suspect that increased Vitamin D and Increased Vitamin D Receptor will PREVENT as well as TREAT many Cancers - Founder of Vitamin D Life Oct 2019
Vitamin D Receptor and Cancers
Items in both categories Vitamin D Receptor and Cancer - Breast:
- Breast cancer associated with Vitamin D Receptor (14th study) – Oct 2019
- After breast cancer treatment 4,000 IU of Vitamin D was not enough to help if have poor Vitamin D receptor – June 2019
- Breast Cancer death 1.8 X more likely if poor Vitamin D Receptor – April 2019
- Breast Cancer and Vitamin D review – March 2018
- Women with Breast Cancer were 16.9 times more likely to have a poor Vitamin D Receptor – Jan 2019
- Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018
- Two chemicals increase the Vitamin D receptor and decrease the growth of breast cancer cells in the lab - March 2018
- Breast Cancer reduces receptor expression and thus block Vitamin D to the cells– July 2017
- Vitamin D receptor as a target for breast cancer therapy (abstract only) – Feb 2017
- Breast Cancer was 4.6 times more likely if have a poor Vitamin D Receptor – Dec 2016
- Increased Breast Cancer metastasis if low vitamin D or poor VDR – Feb 2016
- Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015
- Vitamin D receptor in breasts and breast cancer vary with race – March 2013
- Breast Cancer incidence change by 40 percent with vitamin D receptor genes – Oct 2012
- Genes breast cancer and vitamin D receptor - Sept 2010
Items in both categories Vitamin D Receptor and Cancer - Colon:
- Colorectal Cancer Patients 2.4 X more likely to have poor Vitamin D receptors (less D to cells) – April 2020
- Colorectal cancer linked to poor Vitamin D Receptor (yet again) – Jan 2020
- Colorectal Cancer risk increases when genes reduce the vitamin D levels – Aug 2019
- Risks of Colorectal Cancer, IBD, etc slightly increased if poor Vitamin D Receptor – Aug 2018
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Advanced Colon Cancer risk is doubled or halved with 1000 IU of Vitamin D, depends on Vitamin D Receptors – RCT May 2017
- Colon Cancer survival 3.1 X less likely if poor Vitamin D Receptor – Aug 2017
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- 10 percent of colon cancer linked to Vitamin D Receptor – meta-analysis April 2012
Items in both categories Vitamin D Receptor and Cancer
- How cancer is fought by Vitamin D (Ovarian this time) – Feb 2020
- 8 ways that Cancer might be prevented by Vitamin D - June 2019
- Cancer is leading cause of death - Vitamin D and Receptor activators help
- A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019
- Overview of Vitamin D Actions in Cancer – 31 page chapter in a book – 2018
- Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018
- Vitamin D receptor is essential for both normal and cancerous cells in the lab – June 2018
- Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018
- Cancer and the Vitamin D Receptor, a primer – Sept 2017
- Cancer risks and Vitamin D Receptors – association is unclear – 2017
- Vitamin D, Vitamin D Receptor and Cancer – Nov 2016
- Risk of Cancer increased if poor Vitamin D Receptor – meta-analysis of 73 studies Jan 2016
- Role of Vitamin D in human Diseases and Disorders – An Overview – DBP, VDR June 2014
- Vitamin D Receptor role in Autoimmune Diseases and or cancers – Nov 2013
- Vitamin D receptor polymorphisms are risk factors for various cancers – meta-analysis Jan 2014
Items in both categories Vitamin D Receptor and Cancer - other:
- Blood cell cancer is associated with a 3X worse Vitamin D Receptor – June 2019
- A poor Vitamin D Receptor is associated with many cancers (oral cancer in this case) – Jan 2019
- Endometriosis, Endometrial Cancer, and poor Vitamin D or Receptor – Aug 2018
- Thyroid Cancer rate has increased 3X in 3 decades, Vitamin D Receptor decreases, Calcium increases – Aug 2017
- Gastric Cancer 2.7 X more likely if poor Vitamin D Receptor (Chinese) – 2015
- 2X more likely to survive a form of esophageal cancer in China if have good vitamin D receptor – Feb 2017
- 2X more Thyroid Cancer malignancy if less than 15 ng of vitamin D – June 2012
- Brain cancer in 175 countries related to low UVB and low vitamin D – Oct 2010
Items in both categories Vitamin D Receptor and Cancer - Skin:
- Sunlight, Vitamin D and Skin Cancer Book (3rd edition) - Sept 2020
- Melanoma cancer growth slowed by increased Vitamin D Receptor (yet again) – Oct 2019
- Nonmelanoma Skin Cancer 2X more likely if poor Vitamin D Receptor – Oct 2017
- UVB improvements to Vitamin D receptor appear to improve melanoma survival – Oct 2017
- Skin Cancers, Vitamin D, Vitamin D Receptor and Genes – Jan 2015
- Malignant melanoma may be reduced by skin-activated vitamin D – Nov 2016
- Skin cancer 20 percent more likely with some Vitamin D receptor gene polymorphisms – Oct 2015
- Death from melanoma (without ulcers) greatly decreased if have lots of vitamin D receptors – May 2014
- Melanoma risk 2X to 4X higher if Vitamin D receptor genes had morphed – March 2014
- Vitamin D receptor may suppress skin cancer – Dec 2013
Items in both categories Vitamin D Receptor and Cancer - Prostate:
- Prostate Cancer associated with various genes, including Vitamin D Receptor and CYP24A1 – Nov 2019
- Prostate surgery outcomes vary with Vitamin D Receptors– May 2017
- Prostate cancer in black men is 1.6 times more likely if a poor Vitamin D Receptor – Feb 2017
- Aggressive Prostate Cancer in blacks with low vitamin D – 7X more likely if added Calcium – Jan 2017
- High PSA readings with Prostate Cancer 4 times more likely if poor Vitamin D receptor – March 2016
- 2X less prostate cancer in A-A with low Calcium is due vitamin D receptor gene – July 2013
Items in both categories Vitamin D Receptor and Cancer - Ovarian:
- How cancer is fought by Vitamin D (Ovarian this time) – Feb 2020
- Ovarian Cancer risk reduced if higher vitamin D, more UVB, or better vitamin D receptor – Nov 2018
- Active Vitamin D reduces Ovarian Cancer stem cells growth by 4X (via Vitamin D receptor in lab rat) – March 2018
- Ovarian Cancer in Asia is 1.5 X more likely if poor Vitamin D receptor – meta-analysis Dec 2017
- Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015
- Ovarian Cancer 5.8 X more likely if both low vitamin D and Fok1 gene change – May 2013
Vitamin D makes melanoma cells less aggressive Medical News report on this study
Sathya Muralidhar, Anastasia Filia, Jérémie Nsengimana, Joanna Poźniak, Sally J. O'Shea, Joey M Diaz, Mark Harland, Juliette A. Randerson-Moor, Jörg Reichrath, Jonathan P Laye, Louise van der Weyden, David J. Adams, D.T. Bishop and Julia Newton-Bishop
1α,25-dihydroxyvitamin D3 signals via the Vitamin D Receptor (VDR). Higher serum vitamin D is associated with thinner primary melanoma and better outcome, although a causal mechanism has not been established. As melanoma patients commonly avoid sun exposure, and consequent vitamin D deficiency might worsen outcomes, we interrogated 703 primary melanoma transcriptomes to understand the role of vitamin D-VDR signalling and replicated the findings in TCGA metastases.
VDR expression was independently protective for melanoma death in both primary and metastatic disease.
High tumor VDR expression was associated with upregulation of pathways mediating anti-tumor immunity and correspondingly with higher imputed immune cell scores and histologically detected tumor infiltrating lymphocytes (TILs).
High VDR expressing tumors had downregulation of proliferative pathways, notably Wnt/beta-catenin signaling.
Deleterious low VDR levels resulted from promoter methylation and gene deletion in metastases. Vitamin D deficiency (< 25 nmol/l ~ 10 ng/ml) shortened survival in primary melanoma in a VDR-dependent manner.
In vitro functional validation studies showed that elevated vitamin D-VDR signaling inhibited Wnt/beta-catenin signaling genes. Murine melanoma cells overexpressing VDR produced fewer pulmonary metastases than controls in tail vein metastasis assays.
In summary, vitamin D-VDR signaling contributes to controlling pro-proliferative /immunosuppresive Wnt/beta-catenin signaling in melanoma and this is associated with less metastatic disease and stronger host immune responses.
This is evidence of the causal relationship between vitamin D-VDR signaling and melanoma survival which should be explored as a therapeutic target in primary resistance to checkpoint blockade.