RCP induces Slug expression and cancer cell invasion by stabilizing β1 integrin

M. H. Hwang, K. H. Cho, K. J. Jeong, Y. Y. Park, J. M. Kim, S. L. Yu, C. G. Park, Gordon Mills, H. Y. Lee

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Rab coupling protein (RCP)-induced tumor cell migration has been implicated in tumor pathophysiology and patient outcomes. In the present study, we demonstrate that RCP stabilizes β1 integrin leading to increased β1 integrin levels and activation of a signaling cascade culminating in Slug induction, epithelial-to-mesenchymal transition and increased invasion. Ectopic expression of RCP induced Slug expression. Silencing β1 integrin efficiently inhibited RCP-induced Slug expression and subsequent cancer cell invasion. Conversely, ectopic expression of β1 integrin was sufficient to induce Slug expression. Pharmacological inhibition of integrin linked kinase (ILK), EGFR and NF-κB, as well as transfection of a dominant-negative mutant of Ras (RasN17), significantly inhibited RCP-induced Slug expression and cancer cell invasion. Strikingly, ectopic expression of RCP was sufficient to enhance metastasis of ovarian cancer cells to the lung. Collectively, we demonstrate a mechanism by which RCP promotes cancer cell aggressiveness through sequential β1 integrin stabilization, activation of an ILK/EGFR/Ras/NF-κB signaling cascade and subsequent Slug expression.

Original languageEnglish (US)
Pages (from-to)1102-1111
Number of pages10
JournalOncogene
Volume36
Issue number8
DOIs
StatePublished - Feb 23 2017
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Hwang, M. H., Cho, K. H., Jeong, K. J., Park, Y. Y., Kim, J. M., Yu, S. L., Park, C. G., Mills, G., & Lee, H. Y. (2017). RCP induces Slug expression and cancer cell invasion by stabilizing β1 integrin. Oncogene, 36(8), 1102-1111. https://doi.org/10.1038/onc.2016.277