HUNK suppresses metastasis of basal type breast cancers by disrupting the interaction between PP2A and cofilin-1

Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2622-7. doi: 10.1073/pnas.0914492107. Epub 2010 Jan 22.


Metastasis leads to the death of most cancer patients, and basal breast cancer is the most aggressive breast tumor type. Metastasis involves a complex cell migration process dependent on cytoskeletal remodeling such that targeting such remodeling in tumor cells could be clinically beneficial. Here we show that Hormonally Up-regulated Neu-associated Kinase (HUNK) is dramatically down-regulated in tumor samples and cell lines derived from basal breast cancers. Reconstitution of HUNK expression in basal breast cancer cell lines blocked actin polymerization and reduced cell motility, resulting in decreased metastases in two in vivo murine cancer models. Mechanistically, HUNK overexpression sustained the constitutive phosphorylation and inactivation of cofilin-1 (CFL-1), thereby blocking the incorporation of new actin monomers into actin filaments. HUNK reconstitution in basal breast cancer cell lines prevented protein phosphatase 2-A (PP2A), a phosphatase putatively acting on CFL-1, from binding to CFL-1. Our investigation of HUNK suggests that the interaction between PP2A and CFL-1 may be a target for antimetastasis therapy, particularly for basal breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cofilin 1 / genetics
  • Cofilin 1 / metabolism*
  • Cytoskeleton / metabolism
  • Female
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Male
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Phosphorylation
  • Protein Binding
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • RNA Interference
  • Transplantation, Heterologous


  • Actins
  • Cofilin 1
  • Protein Kinases
  • HUNK protein, human
  • Hunk protein, mouse
  • Protein Serine-Threonine Kinases
  • Protein Phosphatase 2