Zhou Meifeng, Li Xianglu, Wang Weifeng, Wu Jianyong, Tan Jindian
Department of Oncology, Affiliated Cancer Hospital of Hainan Medical University, Hainan Cancer Hospital, Haikou, Hainan, China.
Department of Medical Oncology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, Hainan, China.
Cancer Sci. 2025 Aug;116(8):2281-2295. doi: 10.1111/cas.70064. Epub 2025 May 14.
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.
三阴性乳腺癌（TNBC）的转移通常导致治疗失败。着丝粒蛋白F（CENPF）可诱导TNBC的增殖和转移。然而，CENPF在乳腺癌中的上游机制仍不清楚。采用蛋白质免疫印迹法（Western blot）和逆转录定量聚合酶链反应（RT-qPCR）检测蛋白酶体26S亚基非ATP酶14（PSMD14）、E2F转录因子1（E2F1）和CENPF的水平，并使用Transwell实验评估细胞迁移。此外，应用细胞计数试剂盒8（CCK8）实验研究细胞活力，应用C11-硼二吡咯581/591评估脂质活性氧水平。采用染色质免疫沉淀（ChIP）和双荧光素酶实验检测E2F1与CENPF启动子之间的关联。使用免疫共沉淀（Co-IP）验证PSMD14与E2F1之间的相互作用。敲低CENPF可显著抑制TNBC细胞的迁移和侵袭。此外，CENPF的沉默加剧了花生四烯酸代谢诱导的TNBC细胞铁死亡。同时，敲低E2F1可通过减少其与CENPF启动子的结合，极大地抑制CENPF的表达，并减弱TNBC细胞的侵袭和迁移。更重要的是，PSMD14可通过E2F1/CENPF轴抑制花生四烯酸代谢诱导的TNBC细胞铁死亡。PSMD14/E2F1轴介导的CENPF可通过抑制花生四烯酸代谢诱导的铁死亡促进TNBC的转移。本研究可能为发现缓解TNBC肿瘤转移的方法带来新的见解。
