2. Academic Validation
  3. KIF4A Inhibits Ferroptosis in Glioblastoma via the CHMP4B/GPX4 Axis and Promotes Temozolomide Resistance

KIF4A Inhibits Ferroptosis in Glioblastoma via the CHMP4B/GPX4 Axis and Promotes Temozolomide Resistance

  • Mol Carcinog. 2025 Jul 24. doi: 10.1002/mc.70006.
Xinan Shen 1 2,  Honglei Cheng 3,  Jiarong Zheng 1 2,  Yihan Xia 4,  Yongdong Li 5,  Quanquan Guo 6,  Zhicheng Zhang 5,  Nanheng Yin 5,  Yongshun Liu 2,  Jun Dong 5,  Yuntian Shen 1 2
Affiliations

Affiliations

  • 1 Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 2 Institute of Radiotherapy & Oncology, Soochow University; Suzhou Key Laboratory for Radiation Oncology, Suzhou, China.
  • 3 The First Clinical College, The First Affiliated Hospital, Hainan Medical University, Haikou, China.
  • 4 Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 5 Department of Neurosurgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • 6 The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
PMID: 40705827 DOI: 10.1002/mc.70006
Abstract

Glioblastoma (GBM) is the most malignant primary brain tumor in adults. Temozolomide (TMZ) stands for the first-line chemotherapeutic agent against GBM. TMZ resistance is an important factor contributing to the poor prognosis of GBM, but the underlying molecular mechanisms are unclear. Previous studies have suggested that KIF4A may be an indicator of poor prognosis in glioma patients, but the association of KIF4A with TMZ resistance has never been investigated. The detection of Ferroptosis levels in GBM cells was accomplished through the utilization of ROS, MDA, JC-1, and Western blot analysis. The assessment of TMZ resistance was performed through the implementation of CCK8, cell cloning, and cell cycle analysis. The identification of downstream targets of KIF4A was facilitated by protein profiling and immunofluorescence. KIF4A inhibits Ferroptosis in GBM cells through the CHMP4B/GPX4 axis and promotes TMZ resistance. Knockdown of KIF4A or CHMP4B sensitized GBM cells to chemotherapy. In addition, KIF4A induced epithelial-mesenchymal transition in GBM cells, which synergistically promoted TMZ resistance.The present study elucidates a novel mechanism of TMZ resistance in glioblastoma through the CHMP4B/GPX4 axis. Based on these findings, targeting KIF4A may offer a potential new strategy against GBM.

Keywords

CHMP4B; GPX4; KIF4A; TMZ resistance; ferroptosis; glioblastoma.

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