Direct interaction between CEP85 and STIL mediates PLK4-driven directed cell migration

Yi Liu1,2, Jaeyoun Kim1, Reuben Philip1,2

  • 1Lunenfeld-Tanenbaum Research Institute, University of Toronto, 600 University Avenue, Toronto M5G 1X5, Canada.

Journal of Cell Science
|February 29, 2020
PubMed

Insights

CEP85 and STIL are crucial for cancer cell migration, working with PLK4 to promote movement. Their interaction with PLK4 is essential for directional motility and invasion.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Oncology

Background:

  • Polo-like kinase 4 (PLK4) is overexpressed in many cancers and has an emerging role in cancer cell migration and invasion.
  • The molecular mechanisms underlying PLK4's role in cell motility are not fully understood.
  • Previous research established the CEP85-STIL binding interface's necessity for PLK4 activation and centriole duplication.

Purpose of the Study:

  • To investigate the role of CEP85 and STIL in directional cancer cell migration.
  • To elucidate the molecular mechanisms by which CEP85, STIL, and PLK4 interact to regulate cell motility.

Main Methods:

  • Mutational and functional analyses of CEP85, STIL, and PLK4 interactions.
  • Investigating the recruitment of CEP85 and STIL to the leading edge of migrating cells.
  • Assessing the impact of CEP85 and STIL downregulation on ARP2 phosphorylation and actin cytoskeleton organization.

Main Results:

  • CEP85 and STIL are essential for directional cancer cell migration.
  • The interaction between CEP85, STIL, and PLK4 is critical for effective cell motility.
  • PLK4 recruits CEP85 and STIL to the leading edge, promoting cell protrusion.
  • Downregulation of CEP85 and STIL reduces ARP2 phosphorylation and actin reorganization, impairing migration.

Conclusions:

  • The CEP85-STIL complex plays a significant role in modulating PLK4-driven cancer cell migration.
  • These findings provide molecular insights into the CEP85-STIL complex's function in cancer cell motility.
  • Targeting the CEP85-STIL-PLK4 axis could offer new therapeutic strategies for cancer treatment.

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