UNC0638, a G9a inhibitor, suppresses epithelial-mesenchymal transition-mediated cellular migration and invasion in triple negative breast cancer

Triple-negative breast cancer (TNBC) is associated with an aggressive clinical history, high risk of recurrence and metastasis, and shorter patient survival due to lack of targeted therapy. In the present study, UNC0638, a chemical G9a inhibitor, was identified to suppress TNBC cell invasion and migration in vitro at a non-cytotoxic concentration. In addition, UNC0638 reduced the size and number of the tumorsphere and decreased anchor-independent colony formation in the two TNBC cell lines. Evaluation of the underlying mechanism revealed that the suppressive effect of UNC0638 is associated with modulation of epithelial-mesenchymal transition through enhancing E-cadherin promoter activities and restoring its expression. Thus, the current data indicates that UNC0638 may be developed as a chemotherapeutic agent to effectively treat metastatic cancers, including TNBC.