Suppression of Invasion and Metastasis of Triple-Negative Breast Cancer Lines by Pharmacological or Genetic Inhibition of Slug Activity

• DOI: 10.1016/j.neo.2014.10.006
• Publication Date: 2014-12-09T02:49:13Z
• Authors: Giovanna Ferrari-...; Claudia Chiodoni; Fei Shen; Sara Cattelani; Angela Rachele So...; Gloria Manzotti; Giulia Grisendi; Massimo Dominici; Francesco Rivasi; Mario Paolo Colombo; Alessandro Fatatis; Bruno Calabretta
• Keywords: Slug; Triple-negative breast cancer

Most triple-negative breast cancers (TNBCs) exhibit gene expression patterns associated with epithelial-to-mesenchymal transition (EMT), a feature that correlates propensity for metastatic spread. Overexpression of the EMT regulator Slug is detected in basal and mesenchymal-type TNBCs reduced E-cadherin aggressive disease. The effects depend, part, on interaction its N-terminal SNAG repressor domain chromatin-modifying protein lysine demethylase 1 (LSD1); thus, we investigated whether tranylcypromine [also known as trans-2-phenylcyclopropylamine hydrochloride (PCPA) or Parnate], an inhibitor LSD1 blocks Slug, suppresses migration, invasion, spread TNBC cell lines. We show here PCPA treatment induces other epithelial markers markedly migration invasion lines MDA-MB-231 BT-549. These were phenocopied by silencing. In two models orthotopic cancer, local tumor growth number lung metastases. mice injected directly blood circulation cells, silencing inhibited bone metastases but had no effect infiltration. Thus, blocking activity may suppress and, perhaps, specifically inhibit homing/colonization to bone.