The tetraspanin CD151 is required for Met-dependent signaling and tumor cell growth

Mélanie Franco, Claudia Muratori, Simona Corso, Enrico Tenaglia, Andrea Bertotti, Lorena Capparuccia, Livio Trusolino, Paolo M. Comoglio, Luca Tamagnone

Research output: Contribution to journalArticlepeer-review

Abstract

CD151, a transmembrane protein of the tetraspanin family, is implicated in the regulation of cell-substrate adhesion and cell migration through physical and functional interactions with integrin receptors. In contrast, little is known about the potential role of CD151 in controlling cell proliferation and survival. We have previously shown that β4 integrin, a major CD151 partner, not only acts as an adhesive receptor for laminins but also as an intracellular signaling platform promoting cell proliferation and invasive growth upon interaction with Met, the tyrosine kinase receptor for hepatocyte growth factor (HGF). Here we show that RNAi-mediated silencing of CD151 expression in cancer cells impairs HGF-driven proliferation, anchorage-independent growth, protection from anoikis, and tumor progression in xenograft models in vivo. Mechanistically, we found that CD151 is crucially implicated in the formation of signaling complexes between Met and β4 integrin, a known amplifier of HGF-induced tumor cell growth and survival. CD151 depletion hampered HGF-induced phosphorylation of β4 integrin and the ensuing Grb2-Gab1 association, a signaling pathway leading to MAPK stimulation and cell growth. Accordingly, CD151 knockdown reduced HGF-triggered activation of MAPK but not AKT signaling cascade. These results indicate that CD151 controls Met-dependent neoplastic growth by enhancing receptor signaling through β4 integrin-mediated pathways, independent of cell-substrate adhesion.

Original languageEnglish
Pages (from-to)38756-38764
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number50
DOIs
Publication statusPublished - Dec 10 2010

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'The tetraspanin CD151 is required for Met-dependent signaling and tumor cell growth'. Together they form a unique fingerprint.

Cite this