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Dev Cell. 2014 Sep 8;30(5):553-68. doi: 10.1016/j.devcel.2014.08.006.

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

Author information

1
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy.
2
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, 20141 Milan, Italy.
3
Dipartimento di Scienze Oncologiche, Università degli Studi di Torino, Istituto per la Ricerca e la Cura del Cancro, Strada Provinciale 142 10060 Candiolo, Turin, Italy.
4
Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA.
5
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Dipartimento di Oncologia Sperimentale, Istituto Europeo di Oncologia, 20141 Milan, Italy; Dipartimento di Scienze della Salute, San Paolo, Università degli Studi di Milano, 20122 Milan, Italy.
6
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy. Electronic address: andrea.disanza@ifom.eu.
7
IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20139 Milan, Italy; Dipartimento di Scienze della Salute, San Paolo, Università degli Studi di Milano, 20122 Milan, Italy. Electronic address: giorgio.scita@ifom.eu.

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 in situ 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.

PMID:
25203208
DOI:
10.1016/j.devcel.2014.08.006
[Indexed for MEDLINE]
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