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Article Dans Une Revue Developmental Cell Année : 2016

PRICKLE1 contributes to cancer cell dissemination through its interaction with mTORC2

Résumé

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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Dates et versions

hal-01321061 , version 1 (25-05-2016)

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Avais M Daulat, François Bertucci, Stéphane Audebert, Arnauld Sergé, Pascal Finetti, et al.. PRICKLE1 contributes to cancer cell dissemination through its interaction with mTORC2 . Developmental Cell, 2016, 37, pp.311-325. ⟨10.1016/j.devcel.2016.04.011⟩. ⟨hal-01321061⟩
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