PTPRE promotes gastric cancer cell resistance to 5-fluorouracil by inhibiting ferroptosis via the Src/FAK/TRIB3 axis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42313735.
- Also identified by DOI 10.1371/journal.pone.0351846 and PMC identifier 13278412.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Stomach Neoplasms
- Fluorouracil
- Drug Resistance, Neoplasm
- Ferroptosis
- Protein Serine-Threonine Kinases
- Cell Cycle Proteins
- Repressor Proteins
- Receptor-Like Protein Tyrosine Phosphatases, Class 3