P120 catenin is required for growth factor-dependent cell motility and scattering in epithelial cells

Mauro Cozzolino, Venturina Stagni, Laura Spinardi, Nadia Campioni, Carla Fiorentini, Erica Salvati, Stefano Alemà, Anna Maria Salvatore

Research output: Contribution to journalArticle

Abstract

Cadherin-mediated cell-cell adhesion is dynamically modulated during epithelial-mesenchymal transition triggered by activation of receptor tyrosine kinases (RTK) in epithelial cells. Several cadherin-binding proteins have been identified that control cell-cell adhesion. However, the mechanisms by which intercellular adhesion and cell motility are coregulated are still unknown. Here, we delineate a hitherto uncharted cooperation between RTKs, RhoA GTPase, and p120 catenin in instructing a motile behavior to epithelial cells. We found that expression of an N-terminus-deleted p120 catenin in a variety of epithelial cell types, including primary keratinocytes, effectively competes for endogenous p120 at cadherin binding sites and abrogates EGF-stimulated cell motility as well as HGF-induced cell scattering. The deleted mutant also inhibits the PI3K-dependent RhoA activation ensuing receptor activation. Conversely, we also show that the ectopic expression of full-length p120 in epithelial cells promotes cytoskeletal changes, stimulates cell motility, and activates RhoA. Both motogenic response to p120 and RhoA activation require coactivation of signaling downstream of RTKs as they are suppressed by ablation of the Ras/PI3K pathway. These studies demonstrate that p120 catenin is a necessary target of RTKs in regulating cell motility and help define a novel pathway leading to RhoA activation, which may contribute to the early steps of metastatic invasion.

Original languageEnglish
Pages (from-to)1964-1977
Number of pages14
JournalMolecular Biology of the Cell
Volume14
Issue number5
DOIs
Publication statusPublished - May 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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