PTPRE promotes gastric cancer cell resistance to 5-fluorouracil by inhibiting ferroptosis via the Src/FAK/TRIB3 axis

  • PLoS One. 2026 Jun 18;21(6):e0351846. doi: 10.1371/journal.pone.0351846.
Ming Liu  1 ,  Xiaomei Liao  2 ,  Fangchao Wang  2 ,  Pengqing Jiao  3 ,  Zhongkai Wang  2
Affiliations
  • 1. Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • 2. Department of Pain and Rehabilitation, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
  • 3. Department of Rheumatology and Immunology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China.
PMID: 42313735 DOI: 10.1371/journal.pone.0351846
Abstract

Acquired drug resistance is a major cause of failure in gastric Cancer treatment. The protein tyrosine Phosphatase receptor type E (PTPRE) plays an oncogenic role in certain tumours; however, its function in chemotherapy-resistant gastric Cancer remains unclear. Therefore, we analysed PTPRE expression in gastric Cancer using The Cancer Genome Atlas. In vitro experiments were then conducted to investigate the effects of PTPRE on the resistance of Cancer cells to 5-fluorouracil (5-FU) and its potential mechanisms. The results were further validated in vitro using xenograft studies. We found that PTPRE is upregulated in gastric Cancer tissues and participates in the induction of 5-FU resistance. Mechanistic studies revealed that PTPRE suppressed Ferroptosis in gastric Cancer cells and promoted 5-FU resistance by activating the Src/FAK pathway to upregulate TRIB3 expression. In summary, PTPRE suppresses Ferroptosis in gastric Cancer cells via the Src/FAK/TRIB3 signalling pathway, thereby inducing 5-FU resistance. Intervention with PTPRE and its downstream targets may represent a potential approach for the clinical treatment of 5-FU-resistant gastric Cancer.

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