HMGA1: A Master Regulator of Tumor Progression in Triple-Negative Breast Cancer Cells

• DOI: 10.1371/journal.pone.0063419
• Publication Date: 2013-05-03T05:23:01Z
• Authors: Sandeep N. Shah; Leslie Cope; Weijie Poh; Amy Belton; Sujayita Roy; C. Conover Talbot; Saraswati Sukumar; David L. Huso; Linda M. S. Resar
• Keywords: Reprogramming; Triple-negative breast cancer; Tumor progression

Emerging evidence suggests that tumor cells metastasize by co-opting stem cell transcriptional networks, although the molecular underpinnings of this process are poorly understood. Here, we show for first time high mobility group A1 (HMGA1) gene drives metastatic progression in triple negative breast cancer (MDA-MB-231, Hs578T) reprogramming to a stem-like state. Silencing HMGA1 expression invasive, aggressive dramatically halts growth and results striking morphologic changes from mesenchymal-like, spindle-shaped cuboidal, epithelial-like cells. Mesenchymal genes (Vimentin, Snail) repressed, while E-cadherin is induced knock-down also blocks oncogenic properties, including proliferation, migration, invasion, orthotopic tumorigenesis. Metastatic following mammary implantation almost completely abrogated Moreover, silencing inhibits property three-dimensional mammosphere formation, primary, secondary, tertiary spheres. In addition, depletes initiator/cancer prevents tumorigenesis at limiting dilutions. We discovered an signature highly enriched embryonic Together, these findings indicate master regulator through networks. Future studies needed determine how target therapy.