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

Abstract
We previously identified a SNF1/AMPK-related protein kinase, Hunk, from a mammary tumor arising in an MMTV-neu transgenic mouse. The function of this kinase is unknown. Using targeted deletion in mice, we now demonstrate that Hunk is required for the metastasis of c-myc-induced mammary tumors, but is dispensable for normal development. Reconstitution experiments revealed that Hunk is sufficient to restore the metastatic potential of Hunk-deficient tumor cells, as well as defects in migration and invasion, and does so in a manner that requires its kinase activity. Consistent with a role for this kinase in the progression of human cancers, the human homologue of Hunk is overexpressed in aggressive subsets of carcinomas of the ovary, colon, and breast. In addition, a murine gene expression signature that distinguishes Hunk-wild type from Hunk-deficient mammary tumors predicts clinical outcome in women with breast cancer in a manner consistent with the pro-metastatic function of Hunk in mice. These findings identify a direct role for Hunk kinase activity in metastasis and establish an in vivo function for this kinase.
AuthorsGerald B W Wertheim, Thomas W Yang, Tien-chi Pan, Anna Ramne, Zhandong Liu, Heather P Gardner, Katherine D Dugan, Petra Kristel, Bas Kreike, Marc J van de Vijver, Robert D Cardiff, Carol Reynolds, Lewis A Chodosh
JournalProceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 106 Issue 37 Pg. 15855-60 (Sep 15 2009) ISSN: 1091-6490 [Electronic] United States
PMID19717424 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Protein Kinases
  • SNF1-related protein kinases
  • Hunk protein, mouse
  • Protein Serine-Threonine Kinases
Topics
  • Animals
  • Breast Neoplasms (enzymology, genetics, secondary)
  • Cell Movement (genetics, physiology)
  • Disease-Free Survival
  • Female
  • Gene Expression
  • Humans
  • Mammary Neoplasms, Experimental (enzymology, genetics, secondary)
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Neoplasm Invasiveness (genetics, physiopathology)
  • Neoplasm Metastasis (genetics, physiopathology)
  • Prognosis
  • Protein Kinases (deficiency, genetics, physiology)
  • Protein Serine-Threonine Kinases (deficiency, genetics, physiology)

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