Breast Cancer, Vitamin D, and genes – Welsh
Vitamin D and Breast Cancer: Mechanistic Update
JoEllen Welsh, PhD
The presence of the vitamin D receptor (VDR) in mammary gland and breast cancer has long been recognized, and multiple pre-clinical studies have demonstrated that its ligand 1,25- dihydroxyvitamin D (1,25D) modulates normal mammary gland development and inhibits growth of breast tumors in animal models. Vitamin D deficiency is common in breast cancer patients and some evidence suggests that low vitamin D status enhances the risk for disease development or progression. Although many 1,25D responsive targets in normal mammary cells and in breast cancers have been identified, validation of specific targets that regulate cell cycle, apoptosis, autophagy and differentiation, particularly in vivo, has been challenging. Model systems of carcinogenesis have provided evidence that both VDR expression and 1,25D actions change with transformation, but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive. Because breast cancer is heterogeneous, the relevant VDR targets and potential sensitivity to vitamin D repletion or supplementation will likely differ between patient populations. Detailed analysis of VDR actions in specific molecular subtypes of the disease will be necessary to clarify the conflicting data. Genomic, proteomic and metabolomic analyses of in vitro and in vivo model systems is also warranted to comprehensively understand the network of vitamin D regulated pathways in the context of breast cancer heterogeneity. This review provides an update on recent studies spanning the spectrum of mechanistic (cell/molecular), pre-clinical (animal models) and translational work on the role of vitamin D in breast cancer.
Summary.
Breast cancers are highly heterogeneous, yet many express VDR suggesting that vitamin D status may be clinically relevant for women living with this disease. Mechanistic studies have demonstrated that vitamin D signaling opposes multiple proliferative pathways in both normal breast tissue and in breast cancers, including those driven by reproductive hormones. Recent studies in model systems have highlighted inhibitory effects of vitamin D signaling on EMT and breast cancer stem cells which would be predicted to reduce their capacity to drive metastasis, drug resistance and poor survival. These effects include inhibition of CD44 signaling via disruption of HAS2 production of its ligand HA. In addition, vitamin D has the potential to modulate various non-cancerous cell types in the tumor microenvironment to promote tumor immunity and inhibit tumor angiogenesis. Translation of these findings into prevention or treatment of human breast cancer will require attention to several research gaps including identification of common and relevant VDR targets in distinct breast cancer subtypes, clarification of the mechanisms and importance of accumulation and turnover of vitamin D metabolites in tumors and discovery of regulatory mechanisms that enhance vitamin D signaling in the TME.
📄 Download the PDF from VitaminDWiki
VitaminDWiki
Overview Breast Cancer and Vitamin D
Overview Breast Cancer and Vitamin D
{include}
Breast Cancer and Vitamin D Receptor studies
{category}
Breast Cancer and Vitamin Gene studies
{category}
Studies: Breast Cancer and CYP27B1
{category}
Category listing: Genetics
{include}
Category listing - CYP27B1
{include}
Cancers might alter the CYP24A1 gene
CYP24A1 gene and Vitamin D - many studies
{include}
Vitamin D Receptor category with CANCER in the title (76 as of Feb 2022)
This list is automatically updated
{LIST()}