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cMET promotes metastasis and epithelial‐mesenchymal transition in colorectal carcinoma by repressing RKIP
Author(s) -
Wang Siyun,
Ma Haiqing,
Yan Yan,
Chen Yu,
Fu Sirui,
Wang Junjiang,
Wang Ying,
Chen Hao,
Liu Jianhua
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30142
Subject(s) - gene knockdown , downregulation and upregulation , cancer research , epithelial–mesenchymal transition , metastasis , mapk/erk pathway , colorectal cancer , cell growth , small hairpin rna , cell , kinase , suppressor , biology , cell culture , chemistry , cancer , microbiology and biotechnology , gene , genetics
Increasing evidence indicates that c‐mesenchymal‐epithelial transition factor (cMET) plays an important role in the malignant progression of colorectal cancer (CRC). However, the underlying mechanism is not fully understood. As a metastasis suppressor, raf kinase inhibitory protein (RKIP) loss has been reported in many cancer types. In this study, the expression levels of cMET and RKIP in CRC tissues and cell lines were determined, and their crosstalk and potential biological effects were explored in vitro and in vivo. Our results showed that cMET was inversely correlated with RKIP. Both cMET upregulation and RKIP downregulation indicated poor clinical outcomes. Moreover, the MAPK/ERK signaling pathway was implicated in the regulation of cMET and RKIP. Overexpression of cMET promoted tumor cell epithelial‐mesenchymal transition, invasion, migration, and chemoresistance, whereas the effects could be efficiently inhibited by increased RKIP. Notably, small hairpin RNA‐mediated cMET knockdown dramatically suppressed cell proliferation, although no RKIP‐induced influence on cell growth was observed in CRC. Altogether, cMET overexpression may contribute to tumor progression by inhibiting the antioncogene RKIP, providing preclinical justification for targeting RKIP to treat cMET‐induced metastasis of CRC.