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MARVELD1 modulates cell surface morphology and suppresses epithelial–mesenchymal transition in non‐small cell lung cancer
Author(s) -
Yao Yuanfei,
Shi Ming,
Liu Shanshan,
Li Yiqun,
Guo Kexin,
Ci Yanpeng,
Liu Weizhe,
Li Yu
Publication year - 2016
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22421
Subject(s) - biology , integrin , epithelial–mesenchymal transition , gene silencing , microbiology and biotechnology , microvillus , cell , cancer research , cell adhesion , cancer cell , cancer , metastasis , genetics , gene , membrane
Integrins have been known to play pivotal roles in malignant progression and epithelial–mesenchymal transition (EMT) of non‐small cell lung cancer (NSCLC). We previously demonstrated that MARVELD1, a potential tumor suppressor, is epigenetically silenced in multiple cancer cells. In this study, we found MARVELD1 silencing altered cell surface ultrastructure of NSCLC cells and inhibited the formation of punctate integrin β1/β4 cluster in microvillus, whereas MARVELD1 overexpression suppressed TGF‐β1‐induced EMT. Remarkably, the balance of integrin β1 and β4 was modulated by MARVELD1. MARVELD1 silencing led to imbalance of integrin β1/β4 and significantly reduced microvillus length, furthermore affected the localization of β1/β4 at microvilli tips. TGF‐β1‐induced EMT was promoted by MARVELD1 silencing, while rebalance of integrin β1/β4 partly rescued the epithelial phenotype of MARVELD1‐silenced cells. Mechanistically, we demonstrate that MARVELD1‐mediated balance of integrin β1 and β4 regulates cell surface ultrastructure and EMT phenotype of NSCLC cells, suggesting MARVELD1 has a potential to be developed as a therapeutic target for NSCLC. © 2015 Wiley Periodicals, Inc.