CENPF knockdown inhibits adriamycin chemoresistance in triple-negative breast cancer via the Rb-E2F1 axis

Drug resistance occurs frequently in triple-negative breast cancer (TNBC) and leads to early relapse and short survival. Targeting the 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 that CENPF, which is highly expressed in TNBC, is associated with a poor prognosis in patients receiving chemotherapy. In addition, in vitro CENPF knockdown significantly increased adriamycin (ADR)-induced cytotoxicity in MDA-MB-231 cells and ADR-resistant cells (MDA-MB-231/ADR). Then, we demonstrated that CENPF targets Chk1-mediated G2/M phase arrest and binds to Rb to compete with E2F1 in TNBC. Considering the crucial role of E2F1 in the DNA damage response and DNA repair, a novel mechanism by which CENPF regulates the Rb-E2F1 axis will provide new horizons to overcome chemotherapy resistance in TNBC.

Automated summary

Drug resistance is common in triple-negative breast cancer (TNBC) and leads to poor prognosis. Targeting the DNA damage response (DDR) has shown to be effective in overcoming chemotherapy resistance in TNBC. CENPF, a key regulator of cell cycle progression, is highly expressed in TNBC and is associated with chemotherapy resistance. Knockdown of CENPF increases cytotoxicity in TNBC cells and overcomes adriamycin resistance. CENPF targets the Chk1-mediated G2/M phase arrest and competes with E2F1 in TNBC, providing a novel mechanism to overcome chemotherapy resistance.