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

Oncotarget. 2013 Aug;4(8):1293-308. doi: 10.18632/oncotarget.1136.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / metabolism*
  • Carcinoma, Basal Cell / pathology*
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Epithelial-Mesenchymal Transition
  • Female
  • HMGA1a Protein / genetics
  • HMGA1a Protein / metabolism*
  • Heterografts
  • Humans
  • Mice
  • Mice, SCID
  • Neoplasm Metastasis
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology*
  • Prognosis
  • Signal Transduction
  • Transcriptome

Substances

  • HMGA1a Protein