Open AccessHypoxia-induced vasculogenic mimicry formation in human colorectal cancer cells: Involvement of HIF-1a, Claudin-4, and E-cadherin and Vimentin
Author(s) -
Wen Li,
Shaoqi Zong,
Qi Shi,
HongJia Li,
Jian Xu,
Fenggang Hou
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep37534
Subject(s) - vasculogenic mimicry , vimentin , epithelial–mesenchymal transition , gene knockdown , downregulation and upregulation , cadherin , colorectal cancer , cancer research , metastasis , hypoxia (environmental) , ve cadherin , immunohistochemistry , cell culture , cell , chemistry , biology , medicine , pathology , cancer , gene , biochemistry , organic chemistry , oxygen , genetics
Vasculogenic mimicry (VM) plays an important role in colorectal cancer (CRC) metastasis, and both hypoxia and the epithelial-mesenchymal transition (EMT) are necessary for VM. In this study, HIF-1α expression was upregulated in the VM-positive CRC cell line HCT-116 and thereby affected the expression of the EMT-related markers Claudin-4, E-cadherin (E-cd) and Vimentin(VIM). SB431542 and U0126EtOH, which can inhibit of EMT were used to treat HCT-116 and HCT-8 in these experiments. Both of the inhibitors had significant effect on EMT markers and the formations of VM in CRC cells. In addition, knockdown of HIF-1α in the HCT-116 cells inhibited their capacity for VM. Our study reveals a regulatory role for HIF-1α in VM and suggests that targeting either HIF-1α or EMT may be a valuable strategy for the elimination of CRC metastasis.