PSMD14/E2F1 Axis-Mediated CENPF Promotes the Metastasis of Triple-Negative Breast Cancer Through Inhibiting Ferroptosis

The metastasis of triple-negative breast Cancer (TNBC) usually contributes to the failure of treatment. Centromere Protein F (CENPF) can induce proliferation and metastasis in TNBC. Nevertheless, the upstream mechanism of CENPF in BC remains unclear. Western blot and RT-qPCR were employed for testing the levels of PSMD14, E2F1, and CENPF, and cell migration was assessed using the Transwell assay. Additionally, the CCK8 assay was applied to investigate cell viability, and C11-BODIPY 581/591 was applied to assess the lipid ROS level. ChIP and dual luciferase assays were used to examine the association between E2F1 and the CENPF promoter. The interaction between PSMD14 and E2F1 was verified using Co-IP. Knockdown of CENPF could significantly inhibit migration and invasion in TNBC cells. In addition, the silencing of CENPF aggravated arachidonic acid metabolism-induced Ferroptosis in TNBC cells. Meanwhile, E2F1 knockdown greatly inhibited the expressions of CENPF and attenuated TNBC cell invasion and migration by decreasing its binding with the CENPF promoter. More importantly, PSMD14 could suppress arachidonic acid metabolism-induced Ferroptosis in TNBC cells through the E2F1/CENPF axis. The PSMD14/E2F1 axis-mediated CENPF could promote the metastasis of TNBC by inhibiting arachidonic acid metabolism-induced Ferroptosis. This research might bring novel insights into discovering methods for alleviating tumor metastasis in TNBC.

CENPF; E2F1; PSMD14; TNBC; ferroptosis; metastasis.