HIPK2 downregulates vimentin and inhibits breast cancer cell invasion

Cristina Nodale, Michal Sheffer, Jasmine Jacob-Hirsch, Valentina Folgiero, Rita Falcioni, Aurora Aiello, Alessia Garufi, Gideon Rechavi, David Givol, Gabriella D'Orazi

Research output: Contribution to journalArticlepeer-review

Abstract

Vimentin, a mesenchymal marker, is frequently overexpressed in epithelial carcinomas undergoing epithelial to mesenchymal transition (EMT), a condition correlated with invasiveness and poor prognosis. Therefore, vimentin is a potential molecular target for anticancer therapy. Emerging studies in experimental models underscore the functions of homeodomain-interacting protein kinase 2 (HIPK2) as potential oncosuppressor by acting as transcriptional corepressor or catalytic activator of molecules involved in apoptosis and response to antitumor drugs. However, an involvement of HIPK2 in limiting tumor invasion remains to be elucidated. This study, by starting with a microarray analysis, demonstrates that HIPK2 downregulates vimentin expression in invasive, vimentin-positive, MDA-MB-231 breast cancer cells and in the noninvasive MCF7 breast cancer cells subjected to chemical hypoxia, a drive for mesenchymal shift and tumor invasion. At functional level, vimentin downregulation by HIPK2 correlates with inhibition of breast tumor cell invasion. Together, these data show that vimentin is a novel target for HIPK2 repressor function and that HIPK2-mediated vimentin downregulation can contribute to inhibition of breast cancer cells invasion that might be applied in clinical therapy.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
JournalCancer Biology and Therapy
Volume13
Issue number4
DOIs
StatePublished - 15 Feb 2012

Keywords

  • Breast cancer
  • HIPK2
  • Hypoxia
  • Invasion
  • Tumor suppressor
  • Vimentin

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