2. Academic Validation
  3. DUSP14 suppresses ferroptosis and promotes tumor progression of triple-negative breast cancer

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

  • Cell Rep. 2025 Sep 30;44(10):116365. doi: 10.1016/j.celrep.2025.116365.
Yueyue Cao 1,  Yitian Zheng 2,  Ruiqi Niu 3,  Tingting Wang 3,  Haiyang Yu 3,  Yicheng Tong 4,  Yi-Da Tang 5,  Yueyin Pan 6
Affiliations

Affiliations

  • 1 Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China; Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Clinical Evaluation of Cardiovascular-Kidney-Metabolic and Immuno-Inflammatory Innovative Drugs and Medical Devices, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
  • 2 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Clinical Evaluation of Cardiovascular-Kidney-Metabolic and Immuno-Inflammatory Innovative Drugs and Medical Devices, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China. Electronic address: zhengyitian@bjmu.edu.cn.
  • 3 Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
  • 4 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Clinical Evaluation of Cardiovascular-Kidney-Metabolic and Immuno-Inflammatory Innovative Drugs and Medical Devices, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China.
  • 5 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing Key Laboratory of Clinical Evaluation of Cardiovascular-Kidney-Metabolic and Immuno-Inflammatory Innovative Drugs and Medical Devices, State Key Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing 100191, China. Electronic address: tangyida@bjmu.edu.cn.
  • 6 Department of Medical Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address: panyueyin@ustc.edu.cn.
PMID: 41032417 DOI: 10.1016/j.celrep.2025.116365
Abstract

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.

Keywords

CP: Cancer; DUSP14; PTPN12; ferroptosis; peroxisome proliferator-activated receptors; triple-negative breast cancer.

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