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. 2016 May 23;37(4):311-325.
doi: 10.1016/j.devcel.2016.04.011. Epub 2016 May 12.

PRICKLE1 Contributes to Cancer Cell Dissemination Through Its Interaction With mTORC2

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PRICKLE1 Contributes to Cancer Cell Dissemination Through Its Interaction With mTORC2

Avais M Daulat et al. Dev Cell. .
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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.

Keywords: MINK1; PRICKLE1; cancer cell migration; mTORC2.

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