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

Mol Carcinog. 2016 Nov;55(11):1714-1727. doi: 10.1002/mc.22421. Epub 2015 Oct 28.

Abstract

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.

Keywords: EMT; MARVELD1; NSCLC; cell surface morphology; integrin β1/β4.

MeSH terms

  • A549 Cells
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrin beta1 / metabolism*
  • Integrin beta4 / metabolism*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microvilli / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • ITGB4 protein, human
  • Integrin beta1
  • Integrin beta4
  • MARVELD1 protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • TGFB1 protein, human
  • Transforming Growth Factor beta1