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

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 Cardiff, Carol Reynolds, Lewis A. Chodosh

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)15855-15860
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number37
DOIs
StatePublished - Sep 15 2009

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Phosphotransferases
Breast Neoplasms
Neoplasm Metastasis
AMP-Activated Protein Kinases
Transcriptome
Transgenic Mice
Ovary
Neoplasms
Colon
Breast
SNF1-related protein kinases
Carcinoma

Keywords

  • Breast cancer
  • Knockout mice
  • Mouse models
  • Protein kinase

ASJC Scopus subject areas

  • General

Cite this

Wertheim, G. B. W., Yang, T. W., Pan, T. C., Ramne, A., Liu, Z., Gardner, H. P., ... Chodosh, L. A. (2009). The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis. Proceedings of the National Academy of Sciences of the United States of America, 106(37), 15855-15860. https://doi.org/10.1073/pnas.0906993106

The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis. / Wertheim, Gerald B W; Yang, Thomas W.; Pan, Tien Chi; Ramne, Anna; Liu, Zhandong; Gardner, Heather P.; Dugan, Katherine D.; Kristel, Petra; Kreike, Bas; Van De Vijver, Marc J.; Cardiff, Robert; Reynolds, Carol; Chodosh, Lewis A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 37, 15.09.2009, p. 15855-15860.

Research output: Contribution to journalArticle

Wertheim, GBW, Yang, TW, Pan, TC, Ramne, A, Liu, Z, Gardner, HP, Dugan, KD, Kristel, P, Kreike, B, Van De Vijver, MJ, Cardiff, R, Reynolds, C & Chodosh, LA 2009, 'The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 37, pp. 15855-15860. https://doi.org/10.1073/pnas.0906993106
Wertheim, Gerald B W ; Yang, Thomas W. ; Pan, Tien Chi ; Ramne, Anna ; Liu, Zhandong ; Gardner, Heather P. ; Dugan, Katherine D. ; Kristel, Petra ; Kreike, Bas ; Van De Vijver, Marc J. ; Cardiff, Robert ; Reynolds, Carol ; Chodosh, Lewis A. / The Snf1-related kinase, Hunk, is essential for mammary tumor metastasis. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 37. pp. 15855-15860.
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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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