HMGA1 promotes metastatic processes in basal-like breast cancer regulating EMT and stemness

// Silvia Pegoraro 1 , Gloria Ros 1 , Silvano Piazza 2 , Roberta Sommaggio 3 , Yari Ciani 1,2 , Antonio Rosato 3,4 , Riccardo Sgarra 1 , Giannino Del Sal 1,2 , and Guidalberto Manfioletti 1,* 1 Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy 2 Laboratorio Nazionale CIB, (LNCIB), Area Science Park, Trieste, Italy 3 Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy 4 Istituto Oncologico Veneto IRCCS, Padova, Italy Correspondence: Guidalberto Manfioletti, email: // Keywords : Epithelial to mesenchymal transition, stemness, HMGA1, breast cancer, invasion, metastasis, gene-signature Received : June 28, 2013 Accepted : July 7, 2013 Published : July 9, 2013 Abstract Breast cancer is a heterogeneous disease that progresses to the critical hallmark of metastasis. In the present study, we show that the High Mobility Group A1 (HMGA1) protein plays a fundamental role in this process in basal-like breast cancer subtype. HMGA1 knockdown induces the mesenchymal to epithelial transition and dramatically decreases stemness and self-renewal. Notably, HMGA1 depletion in basal-like breast cancer cell lines reduced migration and invasion in vitro and the formation of metastases in vivo . Mechanistically, HMGA1 activated stemness and key migration-associated genes which were linked to the Wnt/beta-catenin, Notch and Pin1/mutant p53 signalling pathways. Moreover, we identified a specific HMGA1 gene expression signature that was activated in a large subset of human primary breast tumours and was associated with poor prognosis. Taken together, these data provide new insights into the role of HMGA1 in the acquisition of aggressive features in breast cancer.