Open AccessFBXW 7 suppresses epithelial‐mesenchymal transition and chemo‐resistance of non‐small‐cell lung cancer cells by targeting snai1 for ubiquitin‐dependent degradation
Author(s) -
Xiao Guodong,
Li Yuan,
Wang Meng,
Li Xiang,
Qin Sida,
Sun Xin,
Liang Rui,
Zhang Boxiang,
Du Ning,
Xu Chongwen,
Ren Hong,
Liu Dapeng
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12473
Subject(s) - snai1 , epithelial–mesenchymal transition , flow cytometry , cancer research , immunohistochemistry , mtt assay , ubiquitin , suppressor , biology , cell , medicine , cancer , microbiology and biotechnology , immunology , metastasis , biochemistry , genetics , gene
Abstract Objectives FBXW 7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin‐mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW 7 manipulation of NSCLC regeneration and therapy response are not clear. Materials and Methods Immunohistochemical staining and qRT ‐ PCR were applied to detect FBXW 7 and Snai1 expression in 100 samples of NSCLC and matched tumour‐adjacent tissues. FBXW 7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere‐formation assays. Immunofluorescence and co‐immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW 7. Results We detected the decreased FBXW 7 expression in majority of the NSCLC tissues, and lower FBXW 7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW 7 expression tend to have both poorer 5‐year survival outcomes, and shorter disease‐free survival, comparing to those with higher FBXW 7 levels. Functionally, we found that FBXW 7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo‐sensitivity and inhibiting Epithelial‐mesenchymal Transition ( EMT ) progress. Results further showed that FBXW 7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC , which could be partially abrogated by restoring Snai1 expression. Conclusions FBXW 7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC