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.
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Authors | Gerald 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 |
Journal | Proceedings 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 |
PMID | 19717424
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Protein Kinases
- SNF1-related protein kinases
- Hunk protein, mouse
- Protein Serine-Threonine Kinases
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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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