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The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis

Gerald B W Wertheim1, Thomas W Yang, Tien-chi Pan

  • 1Department of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160, USA.

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 2009
PubMed

Insights

The Hunk kinase is essential for mammary tumor metastasis in mice, but not for normal development. Its activity drives cancer cell migration and invasion, and its human counterpart is overexpressed in aggressive human cancers.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Hunk (SNF1/AMPK-related protein kinase) was identified in a mouse mammary tumor.
  • The precise function of Hunk in cancer progression remained unknown.

Purpose of the Study:

  • To elucidate the in vivo function of Hunk kinase in mammary tumor metastasis.
  • To investigate the role of Hunk kinase activity in cancer cell migration and invasion.

Main Methods:

  • Targeted gene deletion in mice to create Hunk-deficient models.
  • Tumorigenesis and metastasis assays in MMTV-neu and c-myc transgenic mice.
  • Reconstitution experiments to assess Hunk's sufficiency for metastatic potential.
  • Analysis of human cancer databases for Hunk homologue expression.
  • Murine gene expression signature analysis correlated with human breast cancer patient outcomes.

Main Results:

  • Hunk is indispensable for the metastasis of c-myc-induced mammary tumors but dispensable for normal development.
  • Hunk kinase activity is required to restore metastatic potential, migration, and invasion in Hunk-deficient tumor cells.
  • The human HUNK homologue is overexpressed in aggressive ovarian, colon, and breast carcinomas.
  • A Hunk-dependent gene expression signature in murine tumors predicts clinical outcome in human breast cancer patients.

Conclusions:

  • Hunk kinase plays a critical, pro-metastatic role in mammary tumor progression.
  • Hunk activity directly promotes cancer cell migration and invasion.
  • Hunk represents a potential therapeutic target for aggressive human carcinomas.

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