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

Cristina Nodale

Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy

Michal Sheffer

Department of Physics of Complex Systems; Weizmann Institute of Science; Rehovot, Israel

Jasmine Jacob-Hirsch

Cancer Research Center; Chaim Sheba Medical Center; Tel-Hashomer and Sachler School of Medicine; Tel-Aviv University; Tel-Aviv, Israel

Valentina Folgiero

Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy

Rita Falcioni

Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy

Aurora Aiello

Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy; Department of Endocrinology; Catholic University; Rome, Italy

Alessia Garufi

Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy

Gideon Rechavi

Cancer Research Center; Chaim Sheba Medical Center; Tel-Hashomer and Sachler School of Medicine; Tel-Aviv University; Tel-Aviv, Israel

David Givol

Department of Molecular Cell Biology; Weizmann Institute of Science; Rehovot, Israel

Gabriella D’Orazi

Corresponding author: gdorazi@unich.it
Department of Experimental Oncology; Molecular Oncogenesis Laboratory; National Cancer Institute “Regina Elena”; Rome, Italy; Department of Oncology and Experimental Medicine; University “G. d’Annunzio”; Chieti, Italy

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.