The Snf1-Related Kinase, Hunk, Is Essential for Mammary Tumor Metastasis
The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis Gerald B. W. Wertheima, Thomas W. Yanga, Tien-chi Pana, Anna Ramnea, Zhandong Liua, Heather P. Gardnera, Katherine D. Dugana, Petra Kristelb, Bas Kreikeb, Marc J. van de Vijverb, Robert D. Cardiffc, Carol Reynoldsd, and Lewis A. Chodosha,1 aDepartments of Cancer Biology, Cell and Developmental Biology, and Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6160; bDepartment of Diagnostic Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands; cCenter for Comparative Medicine, University of California, County Road 98 and Hutchison Drive, Davis, CA 95616; and dDivision of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905 Communicated by Craig B. Thompson, University of Pennsylvania, Philadelphia, PA, July 27, 2009 (received for review April 22, 2009) We previously identified a SNF1/AMPK-related protein kinase, Hunk, Results from a mammary tumor arising in an MMTV-neu transgenic mouse. Hunk Is Overexpressed in Aggressive Subsets of Human Cancers. To The function of this kinase is unknown. Using targeted deletion in investigate its role in human tumorigenesis, we cloned the human mice, we now demonstrate that Hunk is required for the metastasis homologue of Hunk from a fetal brain cDNA library. Sequence of c-myc-induced mammary tumors, but is dispensable for normal analysis yielded a composite cDNA spanning an ORF of 714 amino development. Reconstitution experiments revealed that Hunk is suf- acids (GenBank accession #NM014586). Review of this sequence ficient to restore the metastatic potential of Hunk-deficient tumor and of human genome data indicated that a single Hunk isoform cells, as well as defects in migration and invasion, and does so in a exists that is 92% identical to murine Hunk at the amino acid level manner that requires its kinase activity.
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