83742

MARVELD1

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 beta1/beta4 cluster in microvillus, whereas MARVELD1 overexpression suppressed TGF-beta1-induced EMT. Remarkably, the balance of integrin beta1 and beta4 was modulated by MARVELD1. MARVELD1 silencing led to imbalance of integrin beta1/beta4 and significantly reduced microvillus length, furthermore affected the localization of beta1/beta4 at microvilli tips. TGF-beta1-induced EMT was promoted by MARVELD1 silencing, while rebalance of integrin beta1/beta4 partly rescued the epithelial phenotype of MARVELD1-silenced cells. Mechanistically, we demonstrate that MARVELD1-mediated balance of integrin beta1 and beta4 regulates cell surface ultrastructure and EMT phenotype of NSCLC cells, suggesting MARVELD1 has a potential to be developed as a therapeutic target for NSCLC. (c) 2015 Wiley Periodicals, Inc.CI - (c) 2015 Wiley Periodicals, Inc.