HMGA1 promotes metastatic processes in basal-like breast cancer regulating EMT and stemness.
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.
Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.
Silvia
S
Pegoraro
Gloria
G
Ros
Silvano
S
Piazza
Roberta
R
Sommaggio
Yari
Y
Ciani
Antonio
A
Rosato
Riccardo
R
Sgarra
Giannino
G
Del Sal
Guidalberto
G
Manfioletti
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002280:Basal Cell Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D025741:HMGA1a Protein / Q000235:genetics / Q000378:metabolism*; D064593:Heterografts; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D011379:Prognosis; D015398:Signal Transduction; D059467:Transcriptome
D025741:HMGA1a Protein