Elsevier

Seminars in Cancer Biology

Volume 79, February 2022, Pages 217-230
Seminars in Cancer Biology

Review
An update on vitamin D signaling and cancer

https://doi.org/10.1016/j.semcancer.2020.05.018Get rights and content
Under a Creative Commons license
open access

Abstract

A low vitamin D status is associated with an increased risk of various cancers, such as of colon, breast, prostate and hematological cells. The biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is a high affinity ligand of the transcription factor vitamin D receptor (VDR). 1,25(OH)2D3 induces via VDR changes to the epigenome of healthy and neoplastic cells and in this way influences their transcriptome. Ligand-activated VDR binds to more than 10,000 loci within the human genome and affects the transcription of some 1000 target genes in a large proportion of human tissues and cell types. From the evolutionary perspective, the prime role of vitamin D was probably the control of energy metabolism later shifting to modulate innate and adaptive immunity as well as to regulate calcium and bone homeostasis. Since rapidly growing immune and cancer cells both use the same pathways and genes for controlling their proliferation, differentiation and apoptosis, not surprisingly, vitamin D signaling changes these processes also in neoplastic cells. Thus, anti-cancer effects of vitamin D may derive from managing growth and differentiation in immunity. This review provides an update on the molecular basis of vitamin D signaling, i.e., the effects of 1,25(OH)2D3 on the epigenome and transcriptome, and its relationship to cancer prevention and therapy.

Abbreviations

1,25(OH)2D3
1α,25-dihydroxyvitamin D3, also called calcitriol
25(OH)D3
25-hydroxyvitamin D3, also called calcidiol
AML
acute myeloid leukemia
AMPK
adenosine monophosphate-activated protein kinase (official gene symbol: PRKAA1)
APC
APC regulator of WNT signaling pathway
AXIN2
axin 2
BCL2
BCL2 apoptosis regulator
BRCA1
BRCA1 DNA repair associated
BRD7
bromodomain containing 7
CAF
cancer-associated fibroblast
CCND1
cyclin D1
CDH
cadherin
CDK
cyclin dependent kinase
CDKN
cyclin dependent kinase inhibitor
CEBPA
CCAAT/enhancer binding protein alpha
ChIP-seq
chromatin immunoprecipitation sequencing
CRC
colorectal cancer
CST5
cystatin D
CTCF
CCCTC-binding factor
CTNNB1
catenin beta 1
CXCL8
C-X-C motif chemokine ligand 8, also called IL8
CYP24A1
cytochrome P450 family 24 subfamily A member 1
DKK1
Dickkopf WNT signaling pathway inhibitor 1
EGF
epidermal growth factor
EGFR
epidermal growth factor receptor
ER
estrogen receptor (official gene symbols: ESR1 and ESR2)
FOS
Fos proto-oncogene, AP-1 transcription factor subunit
GABPA
GA binding protein transcription factor subunit alpha
HER2
human epidermal growth factor receptor 2 (official gene symbol: ERBB2)
HOXA9
homeobox A9
ID1
inhibitor of DNA binding 1, HLH protein
IFNG
interferon gamma
IGF
insulin-like growth factor
IL
interleukin
JAK
Janus kinase
JUN
Jun proto-oncogene, AP-1 transcription factor subunit
KDM6B
lysine demethylase 6B
LGR5
leucine rich repeat containing G protein-coupled receptor 5
MAPK14
mitogen-activated protein kinase 14
MECOM
MDS1 and EVI1 complex locus
MEIS1
meis homeobox 1
miR
microRNA
MMP9
matrix metalloprotease 9
MYC
MYC proto-oncogene, BHLH transcription factor
ncRNA
non-coding RNA
NF
normal fibroblast
PBMC
peripheral blood mononuclear cell
Pol II
RNA polymerase II
PR
progesterone receptor (official gene symbol: PGR)
PU.1
purine-rich box 1, Spi-1 proto-oncogene (official gene symbol: SPI1)
PTGER2
prostaglandin E receptor 2
PTGS2
prostaglandin-endoperoxide synthase 2, also called COX2
PTH
parathyroid hormone
RHOA
Ras homolog family member A
RNA-seq
RNA sequencing
RNF43
ring finger protein 43
ROCK1
Rho associated coiled-coil containing protein kinase 1
RPS6KA5
ribosomal protein S6 kinase A5, also called MSK1
RSPO2
R-spondin 2
RXR
retinoid X receptor
SERPINE1
serpin family E member 1, also called plasminogen activator inhibitor (PAI)
SNAI
snail family transcriptional repressor
SPRY2
sprouty RTK signaling antagonist 2
STAT
signal transducers and activators of transcription
TAD
topologically associated domain
TCF7L2
transcription factor 7 like 2
TGFBR1
transforming growth factor beta receptor 1
TH
T helper
TIMP1
TIMP metallopeptidase inhibitor 1
TLR
Toll-like receptor
TNBC
triple-negative breast cancer
TNF
tumor necrosis factor
TNC
tenascin C
Treg
regulatory T
TSS
transcription start site
VDR
vitamin D receptor
VEGFA
vascular endothelial growth factor A
WNT3A
WNT family member 3A

Keywords

Vitamin D
Calcitriol
Vitamin D signaling
VDR
Vitamin D target genes
Chromatin
Epigenome
Immune system
Colon cancer
Prostate cancer
Breast cancer
Hematological malignancies

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