title: HIPK2 downregulates vimentin and inhibits breast cancer cell invasion.
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 non-invasive 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.
authors.affiliation: Department of Experimental Oncology, Molecular Oncogenesis Laboratory, National Cancer Institute "Regina Elena", Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Nodale
authors.forename: Michal
authors.initials: M
authors.lastname: Sheffer
authors.forename: Jasmine
authors.initials: J
authors.lastname: Jacob-Hirsch
authors.forename: Valentina
authors.initials: V
authors.lastname: Folgiero
authors.forename: Rita
authors.initials: R
authors.lastname: Falcioni
authors.forename: Aurora
authors.initials: A
authors.lastname: Aiello
authors.forename: Alessia
authors.initials: A
authors.lastname: Garufi
authors.forename: Gideon
authors.initials: G
authors.lastname: Rechavi
authors.forename: David
authors.initials: D
authors.lastname: Givol
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Orazi
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D014746:Vimentin; C115114:HIPK2 protein, human; D017346:Protein Serine-Threonine Kinases