The CDC42-interacting protein 4 controls epithelial cell cohesion and tumor dissemination

Yannève Rolland, Paola Marighetti, Chiara Malinverno, Stefano Confalonieri, Chiara Luise, Nadia Ducano, Andrea Palamidessi, Sara Bisi, Hiroaki Kajiho, Flavia Troglio, Olga G. Shcherbakova, Alexander R. Dunn, Amanda Oldani, Letizia Lanzetti, Pier Paolo DiFiore, Andrea Disanza, Giorgio Scita

Research output: Contribution to journalArticlepeer-review

Abstract

The role of endocytic proteins and the molecular mechanisms underlying epithelial cell cohesion and tumor dissemination are not well understood. Here, we report that the endocytic F-BAR-containing CDC42-interacting protein 4 (CIP4) is required for ERBB2- and TGF-β1-induced cell scattering, breast cancer (BC) cell motility and invasion into 3D matrices, and conversion from ductal breast carcinoma insitu to invasive carcinoma in mouse xenograft models. CIP4 promotes the formation of an E-cadherin-CIP4-SRC complex that controls SRC activation, E-cadherin endocytosis, and localized phosphorylation of the myosin light chain kinase, thereby impinging on the actomyosin contractility required to generate tangential forces to break cell-cell junctions. CIP4 is upregulated in ERBB2-positive human BC, correlates with increased distant metastasis, and is an independent predictor of poor disease outcome in subsets of BC patients. Thus, it critically controls cell-cell cohesion and is required for the acquisition of an invasive phenotype in breast tumors.

Original languageEnglish
Pages (from-to)553-568
Number of pages16
JournalDevelopmental Cell
Volume30
Issue number5
DOIs
Publication statusPublished - Sep 8 2014

ASJC Scopus subject areas

  • Developmental Biology

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