2. Academic Validation
  3. SOX4 induces cisplatin resistance in cervical cancer cells by inhibiting aerobic glycolysis

SOX4 induces cisplatin resistance in cervical cancer cells by inhibiting aerobic glycolysis

  • Cell Death Discov. 2026 Mar 14;12(1):263. doi: 10.1038/s41420-026-02954-x.
Ruili Sun # 1 2 3 4,  Haofei Gong # 1 2 4,  Ran Zhao 1 2 3 4,  Huiying Lv 1 2 4,  Huijie Yang 1 2,  Xiaofei Zhu 1 4 5,  Xinlai Qian 6,  Jian Li 7,  Qiongzi Wang 8 9
Affiliations

Affiliations

  • 1 Henan International Joint Laboratory of Immunology and Model Animals, School of Medical Technology, Xinxiang Medical University, Xinxiang, China.
  • 2 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
  • 3 Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 4 Xinxiang Key Laboratory of Tumor Microenvironment and Immunotherapy, Xinxiang Medical University, Xinxiang, China.
  • 5 Department of Clinical Laboratory, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 6 Department of Pathology, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [email protected].
  • 7 Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [email protected].
  • 8 Henan International Joint Laboratory of Immunology and Model Animals, School of Medical Technology, Xinxiang Medical University, Xinxiang, China. [email protected].
  • 9 Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China. [email protected].
  • # Contributed equally.
PMID: 41832199 DOI: 10.1038/s41420-026-02954-x
Abstract

Cisplatin resistance remains a major cause of chemotherapy failure in cervical Cancer. Although our previous work identified that SOX4 promotes cisplatin resistance in cervical Cancer cells, the underlying mechanism has not been fully elucidated. Here, we demonstrated that SOX4 not only induces resistance to cisplatin but also to oxaliplatin and carboplatin, suggesting its potential role as a multidrug resistance gene. Overexpression of SOX4 markedly suppressed glycolytic activity in cervical Cancer cells and induced cisplatin resistance by inhibiting both the intrinsic and extrinsic apoptotic pathways. Rescue and neutralization experiments further indicated that SOX4 upregulates SIRT1, which subsequently represses the expression of GLUT1 on the cell membrane. This suppression leads to diminished cellular glucose uptake, resulting in decreased glycolysis and overall metabolic activity. Given that cisplatin preferentially targets highly proliferating cells, SOX4-driven metabolic deceleration enables cervical Cancer cells to evade cisplatin-mediated cytotoxicity. Together, these findings demonstrate that SOX4 enhances cisplatin resistance in cervical Cancer through SIRT1-upregulated suppression of glycolysis.

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