@article{b2e3b2e01a40486b89be34ec7e3d7ddf,
title = "Vitamin D Deficiency Promotes Liver Tumor Growth in Transforming Growth Factor-β/Smad3-Deficient Mice Through Wnt and Toll-like Receptor 7 Pathway Modulation",
abstract = "Disruption of the TGF-β pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-β signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3+/- mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-β pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-β pathway member expression levels and β-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-β member expression with lower β-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-β pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and β-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling.",
author = "Jian Chen and Katz, {Lior H.} and Mu{\~n}oz, {Nina M.} and Shoujun Gu and Shin, {Ji Hyun} and Jogunoori, {Wilma S.} and Lee, {Mi Hye} and Belkin, {Mitchell D.} and Kim, {Sang Bae} and White, {Jon C.} and Jaclyn Andricovich and Alexandros Tzatsos and Shulin Li and Kim, {Sang Soo} and Kirti Shetty and Bibhuti Mishra and Asif Rashid and Lee, {Ju Seog} and Lopa Mishra",
year = "2016",
month = jul,
day = "26",
doi = "10.1038/srep30217",
language = "אנגלית",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}