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.

Oncogene
|June 16, 2009
PubMed

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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