DUSP14 suppresses ferroptosis and promotes tumor progression of triple-negative breast cancer

作者：Yueyue Cao, Yitian Zheng, Ruiqi Niu, Tingting Wang, Haiyang Yu, Yicheng Tong, Yida Tang, Yueyin Pan · 发表于：Cell Reports · 年份：2025 · DOI：10.1016/j.celrep.2025.116365 · 被引用次数：5 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Cancer-related gene regulation

Triple-negative breast cancer (TNBC) treatment remains challenging. Here, we found that dual-specificity phosphatase 14 (DUSP14) is highly expressed in TNBC and is associated with shorter relapse-free survival in patients. DUSP14 knockdown effectively inhibited the proliferation, migration, and invasion of TNBC cells in vitro and significantly suppressed tumor growth in vivo. Mechanistically, DUSP14 knockdown increased phosphorylation of protein tyrosine phosphatase non-receptor type 12 (PTPN12), thereby inhibiting the transcriptional activity of peroxisome proliferator-activated receptor alpha (PPARα) and ultimately downregulating the expression of stearoyl-coenzyme A (CoA) desaturase (SCD), a target gene involved in tumor progression and chemoresistance. This mechanism promoted lipid peroxidation in breast cancer cells, triggering ferroptotic cell death. In clinical analyses, DUSP14 and SCD protein levels in TNBC were strongly correlated. Targeting the DUSP14-PTPN12-PPARα/SCD axis with a small-molecule drug effectively restricted the malignant phenotype of TNBC cells. These findings reveal the role of DUSP14 in regulating ferroptosis. Targeting DUSP14 represents a promising strategy for TNBC treatment.