PRICKLE1 Contributes to Cancer Cell Dissemination through Its Interaction with mTORC2.

Autor:	Daulat AM; Inserm, U1068, CRCM, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France., Bertucci F; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France., Audebert S; Inserm, U1068, CRCM, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France., Sergé A; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, Leuko/Stromal Interactions, Marseille 13009, France., Finetti P; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France., Josselin E; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, TrGET Platform, Marseille 13009, France., Castellano R; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, TrGET Platform, Marseille 13009, France., Birnbaum D; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France; Inserm, U1068, CRCM, Molecular Oncology 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France., Angers S; Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON M5S3M2, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, ON M5S1A8, Canada., Borg JP; Inserm, U1068, CRCM, Cell Polarity, Cell Signalling and Cancer 'Equipe labellisée Ligue Contre le Cancer', Marseille 13009, France; Institut Paoli-Calmettes, Marseille 13009, France; Aix-Marseille Université, UM 105, Marseille 13284, France; CNRS, UMR7258, CRCM, Marseille 13009, France. Electronic address: jean-paul.borg@inserm.fr.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2016 May 23; Vol. 37 (4), pp. 311-325. Date of Electronic Publication: 2016 May 12.
DOI:	10.1016/j.devcel.2016.04.011
Abstrakt:	Components of the evolutionarily conserved developmental planar cell polarity (PCP) pathway were recently described to play a prominent role in cancer cell dissemination. However, the molecular mechanisms by which PCP molecules drive the spread of cancer cells remain largely unknown. PRICKLE1 encodes a PCP protein bound to the promigratory serine/threonine kinase MINK1. We identify RICTOR, a member of the mTORC2 complex, as a PRICKLE1-binding partner and show that the integrity of the PRICKLE1-MINK1-RICTOR complex is required for activation of AKT, regulation of focal adhesions, and cancer cell migration. Disruption of the PRICKLE1-RICTOR interaction results in a strong impairment of breast cancer cell dissemination in xenograft assays. Finally, we show that upregulation of PRICKLE1 in basal breast cancers, a subtype characterized by high metastatic potential, is associated with poor metastasis-free survival. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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