CENPF Knockdown Inhibits Adriamycin Chemoresistance in Triple Negative Breast Cancer mediated by Rb-E2F1-Chk1 Axis

Abstract Frequent developed resistance leads to early relapse and short survival in Triple-negative breast cancer (TNBC). Targeting DNA damage response (DDR) has become an effective strategy for overcoming TNBC chemoresistance. CENPF (centromere protein) is a key regulator of cell cycle progression, but its role in TNBC chemotherapy resistance remains unclear. Here we found CENPF, highly expressed in TNBC, is associated with poor prognosis in patients receiving chemotherapy. And in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 and its ADR-resistant strains (MDA-MB-231/ADR). Then we demonstrated that Rb-E2F1 axis mediates regulation of CENPF on Chk1 (Check Point kinase1) expression and CENPF promotes adriamycin chemoresistance by inducing Chk1-mediated G2/M phase arrest in TNBC. Collectively, our results indicated a novel mechanism of CENPF to regulate TNBC chemoresistance through Rb-E2F1-Chk1 axis and also suggested CENPF as a potential target for intervention to overcome chemotherapy resistance in TNBC.