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J Cell Sci. 2020 Feb 27. pii: jcs.238352. doi: 10.1242/jcs.238352. [Epub ahead of print]

Direct interaction between CEP85 and STIL mediates PLk4-driven directed cell migration.

Author information

1
Lunenfeld-Tanenbaum Research Institute, University of Toronto, 600 University Avenue, Toronto M5G 1X5, Canada.
2
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
3
Donnelly Centre and Banting and Best Department of Medical Research, University of Toronto, 160 College Street, Toronto, ON M5S 1A8, Canada.
4
Medical Research Council - Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
5
Lunenfeld-Tanenbaum Research Institute, University of Toronto, 600 University Avenue, Toronto M5G 1X5, Canada pelletier@lunenfeld.ca.

Abstract

PLK4 has emerged as a prime target for cancer therapeutics and its overexpression is frequently observed in various types of human cancer. Recent studies have further revealed an unexpected oncogenic activity of PLK4 in regulating cancer cell migration and invasion. However, the molecular basis behind PLK4's role in these processes still remains only partly understood. Our previous work demonstrated that an intact CEP85-STIL binding interface is necessary for robust PLK4 activation and centriole duplication. Here we show that CEP85 and STIL are also required for directional cancer cell migration. Mutational and functional analyses reveal that the interactions between CEP85, STIL and PLK4 are essential for effective directional cell motility. Mechanistically, we show that PLK4 can drive the recruitment of CEP85 and STIL at the leading edge of cells to promote protrusive activity, and that downregulation of CEP85 and STIL leads to a reduction in ARP2 phosphorylation and reorganization of the actin cytoskeleton, which in turn impairs cell migration. Collectively, our studies provide molecular insight into the important role of the CEP85-STIL complex in modulating PLK4 driven cancer cell migration.

KEYWORDS:

Cell motility and actin; Centriole; Centrosomes

PMID:
32107292
DOI:
10.1242/jcs.238352

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