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Smad4 Inhibits VEGF‐A and VEGF‐C Expressions via Enhancing Smad3 Phosphorylation in Colon Cancer
Author(s) -
Li Xuemei,
Li Xinlei,
Lv Xiaohong,
Xiao Jianbing,
Liu Baoquan,
Zhang Yafang
Publication year - 2017
Publication title -
the anatomical record
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.678
H-Index - 62
eISSN - 1932-8494
pISSN - 1932-8486
DOI - 10.1002/ar.23610
Subject(s) - colorectal cancer , cancer research , apoptosis , vascular endothelial growth factor , metastasis , phosphorylation , cancer , biology , cell growth , transforming growth factor , cell migration , cancer cell , in vivo , in vitro , medicine , vegf receptors , microbiology and biotechnology , biochemistry
Smad4 is a critical factor in the TGF‐β pathway and is involved in tumor progression and metastasis, but the role of Smad4 in colon cancer cells is unclear. The aim of this study is to explore the effect and the underlying mechanism of Smad4 on the growth, migration and apoptosis of colon cancer cells as well as vascular endothelial growth factor (VEGF)‐A and VEGF‐C secreted by these cells. In this study, we showed that Smad4, VEGF‐A, and VEGF‐C are independent prognostic factors of colon cancer, and Smad4 expression was negatively correlated with VEGF‐A and ‐C in samples. We found that Smad4 mRNA and protein levels in colon cancer cells, particularly in HCT‐116 cells, were significantly lower than those in the human intestinal epithelial cell line (HIEC). Smad4 overexpression promoted tumor cell apoptosis, inhibited VEGF‐A and ‐C expression in vitro and in vivo , but had no effect on cell proliferation and migration. Tail vein injection of the virus inhibited xenograft growth in nude mice. Importantly, we also demonstrated that Smad4 could increase the phosphorylation level of Smad3, but not Smad2, which may be one of the mechanisms underlying these effects of Smad4 in colon cancer. Therefore, Smad4 may be a new target for the treatment of colon cancer. Anat Rec, 300:1560–1569, 2017. © 2017 Wiley Periodicals, Inc.