Cofilin drives cell-invasive and metastatic responses to TGF-β in prostate cancer

Joanne Collazo, Beibei Zhu, Spencer Larkin, Sarah K. Martin, Hong Pu, Craig Horbinski, Shahriar Koochekpour, Natasha Kyprianou*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

59 Scopus citations

Abstract

Cofilin (CFL) is an F-Actin-severing protein required for the cytoskeleton reorganization and filopodia formation, which drives cell migration. CFL binding and severing of F-Actin is controlled by Ser3 phosphorylation, but the contributions of this step to cell migration during invasion and metastasis of cancer cells are unclear. In this study, we addressed the question in prostate cancer cells, including the response to TGF-β, a critical regulator of migration. In cells expressing wild-type CFL, TGF-β treatment increased LIMK-2 activity and cofilin phosphorylation, decreasing filopodia formation. Conversely, constitutively active CFL (SerAla) promoted filipodia formation and cell migration mediated by TGF-β. Notably, in cocultures of prostate cancer epithelial cells and cancer-Associated fibroblasts, active CFL promoted invasive migration in response to TGF-β in the microenvironment. Further, constitutively active CFL elevated the metastatic ability of prostate cancer cells in vivo. We found that levels of active CFL correlated with metastasis in a mouse model of prostate tumor and that in human prostate cancer, CFL expression was increased significantly in metastatic tumors. Our findings show that the actin-severing protein CFL coordinates responses to TGF-β that are needed for invasive cancer migration and metastasis.

Original languageEnglish (US)
Pages (from-to)2362-2373
Number of pages12
JournalCancer Research
Volume74
Issue number8
DOIs
StatePublished - Apr 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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