Related Experiment Video
Updated: Dec 27, 2025

Measuring Cell-Edge Protrusion Dynamics during Spreading using Live-Cell Microscopy
Published on: November 1, 2021
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.
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 the role of PLK4 in these processes still remains only partly understood. Our previous work has 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 to the leading edge of cells to promote protrusive activity, and that downregulation of CEP85 and STIL leads to a reduction in ARP2 (also known as ACTR2) 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.This article has an associated First Person interview with the first author of the paper.
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.
Related Concept Videos
Cytoskeletal Coordination in Cell Migration
Cell Polarization by Rho Proteins
Mechanism of Filopodia Formation
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Cell Motility through Blebbing
Blebbing Through the Matrix
In multicellular...
Cell Migration
Mechanism of Lamellipodia Formation

