2. Academic Validation
  3. P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker

P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker

  • Oncogenesis. 2024 Nov 23;13(1):42. doi: 10.1038/s41389-024-00541-2.
Zheng Yuan # 1,  Hongbo Jing # 1,  Yilin Deng # 1 2,  Meichen Liu # 1 2,  Tao Jiang 3,  Xiong Jin 1,  Weiwei Lin 4,  Yang Liu 5 6,  Jinlong Yin 7 8
Affiliations

Affiliations

  • 1 Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China.
  • 2 Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, 10408, Republic of Korea.
  • 3 Medical Innovation Research Division of Chinese PLA General Hospital, Beijing, 100853, China.
  • 4 Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou, 450052, China. linweiwei@zzu.edu.cn.
  • 5 Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China. liuyang.jcbi@henu.edu.cn.
  • 6 Huaihe Hospital of Henan University, Kaifeng, 475004, China. liuyang.jcbi@henu.edu.cn.
  • 7 Henan Key Laboratory of Brain Targeted Bio-nanomedicine, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China. jlyin@henu.edu.cn.
  • 8 Huaihe Hospital of Henan University, Kaifeng, 475004, China. jlyin@henu.edu.cn.
  • # Contributed equally.
PMID: 39580454 DOI: 10.1038/s41389-024-00541-2
Abstract

Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway. Transcriptional silencing of P4HB induces Apoptosis and diminishes stem cell-like characteristics in GSCs. Treatments with the chemical CCF624 or the China National Medical Products Administration (NMPA)-approved securinine significantly prolonged survival in patient-derived xenograft mouse models, underscoring P4HB's potential as a therapeutic target and presenting an expedited path to clinical application through drug repurposing. Additionally, elevated P4HB levels in patient serum were found to correlate with disease progression, underscoring its utility as a biomarker and its promise for precision medicine.

Figures
Products