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Updated: Jun 22, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
Published on: April 2, 2020
The Ste20-like kinase SLK is required for ErbB2-driven breast cancer cell motility
K Roovers1, S Wagner, C J Storbeck
1Centre for Cancer Therapeutics, Ottawa Health Research Institute, Ontario, Canada.
Abstract:
The Ste20-like kinase, SLK, is involved in the control of cell motility through its effects on actin reorganization and focal adhesion turnover. Here we investigated the role of SLK in chemotaxis downstream of the tyrosine kinase receptor, HER2/ErbB2/Neu, which is frequently overexpressed in human breast cancers. Our results show that SLK is required for the efficient cell migration of human and mouse mammary epithelial cell lines in the presence of the Neu activator, heregulin, as a chemoattractant. SLK activity is stimulated by heregulin treatment or by overexpression of activated Neu. Phosphorylation of tyrosine 1201 or tyrosines 1226/7 on Neu is a key event for SLK activation and cell migration, and cancer cell invasion mediated by these tyrosines is inhibited by kinase-inactive SLK. Signaling pathway inhibitors show that Neu-mediated SLK activation is dependent on MEK, PI3K, PLCgamma and Shc signaling. Furthermore, heregulin-stimulated SLK activity requires signals from the focal adhesion proteins, FAK and src. Finally, phospho-FAK analysis shows that SLK is required for Neu-dependent focal adhesion turnover. Together, these studies define an interaction between Neu and SLK signaling in the regulation of cancer cell motility.
Insights
The Ste20-like kinase (SLK) regulates cancer cell migration downstream of HER2/ErbB2/Neu. SLK activation by heregulin is crucial for mammary epithelial cell movement and invasion, involving key signaling pathways.
Area of Science:
- Cell Biology
- Molecular Oncology
- Signal Transduction
Background:
- The Ste20-like kinase (SLK) plays a role in cell motility by influencing actin reorganization and focal adhesion turnover.
- HER2/ErbB2/Neu, a tyrosine kinase receptor, is often overexpressed in human breast cancers and implicated in cell migration.
Purpose of the Study:
- To investigate the role of SLK in chemotaxis mediated by the HER2/ErbB2/Neu receptor.
- To elucidate the signaling pathways linking Neu activation to SLK-dependent cell migration and invasion.
Main Methods:
- Utilized human and mouse mammary epithelial cell lines.
- Assessed cell migration and invasion in response to heregulin (Neu activator).
- Employed signaling pathway inhibitors and phospho-FAK analysis to study SLK activation and focal adhesion dynamics.
Main Results:
- SLK is essential for efficient cell migration and invasion stimulated by heregulin or activated Neu.
- Neu phosphorylation at specific tyrosines (1201 or 1226/7) is critical for SLK activation and migration.
- Neu-mediated SLK activation depends on MEK, PI3K, PLCgamma, and Shc signaling, as well as focal adhesion proteins FAK and src.
- SLK is required for Neu-dependent focal adhesion turnover.
Conclusions:
- SLK acts downstream of HER2/ErbB2/Neu signaling to regulate cancer cell motility.
- This study defines a novel interaction between Neu and SLK signaling pathways in controlling cancer cell migration and invasion.
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