Silencing the HMGA1 Gene Blocks Metastasis in Breast Cancer

Blocking the activity of the protein encoded by the HMGA1 (high mobility group A1) gene in breast cancer cells renders them less aggressive and diminishes their ability to metastasize.

Investigators at Johns Hopkins University (Baltimore, MD, USA) have been studying the role of HMGA1 in cancer growth and spread for more than 20 years. In the current paper, they described experiments with "triple negative" breast cancer cells—those that lack hormone receptors or HER2 gene amplification—in which HMGA1 expression had been silenced.

They reported in the May 2, 2013, online edition of the journal PLOS ONE that silencing HMGA1 expression in the aggressive, invasive triple negative breast cancer cells dramatically halted cell growth and resulted in striking morphologic changes from mesenchymal-like, spindle-shaped cells to cuboidal, epithelial-like cells. Mesenchymal genes were repressed, while E-cadherin was induced in the cells that lacked HMGA1 expression. Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis. E-cadherin down regulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.