Unknown,Transcriptomics,Genomics,Proteomics

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The Snf1-Related Kinase, Hunk, Is Essential for Mammary Tumor Metastasis


ABSTRACT: We previously identified a novel 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 Hunk 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. Together, these findings establish a role for Hunk in metastasis and an in vivo function for this kinase. Hunk-deficient animals were crossed to mice harboring an MMTV-c-myc transgene (Leder et al., 1986). Hunk heterozygous, MMTV-c-myc mice were backcrossed to Hunk heterozygous animals. MMTV-c-myc female animals of each Hunk genotype were mated twice, then monitored twice weekly for mammary tumors. Mice possessing tumors with a maximum diameter of 20 mm were sacrificed and organs were examined at necropsy. Tumor nodules were identified by examination of organs through a Leica Wild MZ8 dissection microscope.

ORGANISM(S): Mus musculus

SUBMITTER: Lewis Chodosh 

PROVIDER: E-GEOD-14226 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Wertheim Gerald B W GB   Yang Thomas W TW   Pan Tien-chi TC   Ramne Anna A   Liu Zhandong Z   Gardner Heather P HP   Dugan Katherine D KD   Kristel Petra P   Kreike Bas B   van de Vijver Marc J MJ   Cardiff Robert D RD   Reynolds Carol C   Chodosh Lewis A LA  

Proceedings of the National Academy of Sciences of the United States of America 20090828 37


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  ...[more]

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