MARVELD1 modulates cell surface morphology and suppresses epithelial-mesenchymal transition in non-small cell lung cancer

详细信息    查看全文

• 作者：Yuanfei Yao ; Ming Shi ; Shanshan Liu ; Yiqun Li ; Kexin Guo ; Yanpeng Ci ; Weizhe Liu and Yu Li
• 刊名：Molecular Carcinogenesis
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：55
• 期：11
• 页码：1714-1727
• 全文大小：9581K
• ISSN：1098-2744

文摘

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.