Vitamin D-VDR Signaling Inhibits Wnt/β-Catenin-Mediated Melanoma Progression and Promotes Antitumor Immunity

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 patients with melanoma commonly avoid sun exposure, and consequent vitamin D deficiency...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2019-12, Vol.79 (23), p.5986-5998
Main Authors: Muralidhar, Sathya, Filia, Anastasia, Nsengimana, Jérémie, Poźniak, Joanna, O'Shea, Sally J, Diaz, Joey M, Harland, Mark, Randerson-Moor, Juliette A, Reichrath, Jörg, Laye, Jonathan P, van der Weyden, Louise, Adams, David J, Bishop, D T, Newton-Bishop, Julia
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Calcitriol - blood
Calcitriol - deficiency
Cell Line, Tumor
Datasets as Topic
Disease Progression
Female
Humans
Lymphocytes, Tumor-Infiltrating - immunology
Male
Melanoma - blood
Melanoma - immunology
Melanoma - mortality
Melanoma - pathology
Mice
Receptors, Calcitriol - metabolism
Skin - metabolism
Skin Neoplasms - blood
Skin Neoplasms - immunology
Skin Neoplasms - mortality
Skin Neoplasms - pathology
Survival Analysis
Time Factors
Vitamin D Deficiency - blood
Vitamin D Deficiency - immunology
Vitamin D Deficiency - pathology
Wnt Signaling Pathway
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Summary: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 patients with melanoma 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 signaling and replicated the findings in The Cancer Genome Atlas metastases. expression was independently protective for melanoma-related death in both primary and metastatic disease. High tumor expression was associated with upregulation of pathways mediating antitumor immunity and corresponding with higher imputed immune cell scores and histologically detected tumor-infiltrating lymphocytes. High -expressing tumors had downregulation of proliferative pathways, notably Wnt/β-catenin signaling. Deleterious low levels resulted from promoter methylation and gene deletion in metastases. Vitamin D deficiency (
ISSN:0008-5472
1538-7445
1538-7445
DOI:10.1158/0008-5472.CAN-18-3927