The serine/threonine kinase MINK1 directly regulates the function of promigratory proteins - Archive ouverte HAL Access content directly
Journal Articles Journal of Cell Science Year : 2022

The serine/threonine kinase MINK1 directly regulates the function of promigratory proteins

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1
Avais Daulat
Mônica Wagner
  • Function : Author
Stéphane Audebert
Malgorzata Kowalczewska
  • Function : Author
Jeremy Ariey-Bonnet
François Bertucci
  • Function : Author
Luc Camoin

Abstract

ABSTRACT Upregulation of the developmental Wnt planar cell polarity (Wnt/PCP) pathway is observed in many cancers and is associated with cancer development. We have recently shown that PRICKLE1, a core Wnt/PCP pathway component, is a marker of poor prognosis in triple-negative breast cancer (TNBC). PRICKLE1 is phosphorylated by the serine/threonine kinase MINK1 and contributes to TNBC cell motility and invasiveness. However, the identity of the substrates of MINK1 and the role of MINK1 enzymatic activity in this process remain to be addressed. We used a phosphoproteomic strategy to identify MINK1 substrates, including LL5β (also known as PHLDB2). LL5β anchors microtubules at the cell cortex through its association with CLASP proteins to trigger focal adhesion disassembly. LL5β is phosphorylated by MINK1, promoting its interaction with CLASP proteins. Using a kinase inhibitor, we demonstrate that the enzymatic activity of MINK1 is involved in PRICKLE1–LL5β complex assembly and localization, as well as in cell migration. Analysis of gene expression data reveals that the concomitant upregulation of levels of mRNA encoding PRICKLE1 and LL5β, which are MINK1 substrates, is associated with poor metastasis-free survival in TNBC patients. Taken together, our results suggest that MINK1 may represent a potential target for treatment of TNBC.

Dates and versions

hal-03792746 , version 1 (30-09-2022)

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Avais Daulat, Mônica Wagner, Stéphane Audebert, Malgorzata Kowalczewska, Jeremy Ariey-Bonnet, et al.. The serine/threonine kinase MINK1 directly regulates the function of promigratory proteins. Journal of Cell Science, 2022, 135 (17), ⟨10.1242/jcs.259347⟩. ⟨hal-03792746⟩
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