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

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          Abstract

          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.

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          Author and article information

          Journal
          Dev. Cell
          Developmental cell
          Elsevier BV
          1878-1551
          1534-5807
          May 23 2016
          : 37
          : 4
          Affiliations
          [1 ] 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.
          [2 ] 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.
          [3 ] 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.
          [4 ] 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.
          [5 ] 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.
          [6 ] 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.
          Article
          S1534-5807(16)30231-3
          10.1016/j.devcel.2016.04.011
          27184734
          7e7015c7-2af1-4ec7-9524-99b5713673e4
          History

          MINK1,PRICKLE1,cancer cell migration,mTORC2
          MINK1, PRICKLE1, cancer cell migration, mTORC2

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