Hypoxia‐induced PGK1 expression promotes esophageal squamous cell carcinoma progression via stimulating MYH9‐mediated GSK3β/β‐catenin signalling
PMCID: PMC12177104
PMID: 40534132
DOI: 10.1002/ctm2.70376
Journal: Clinical and translational medicine
Publication Date: 2025-6-18
Authors: Xu J, Wu L, Chen T, Liu Y, Zhang Y, et al.
Key Points
- Elevated PGK1 levels correlate with poor survival and advanced tumor stages in ESCC patients
- PGK1 promotes tumor progression through MYH9-mediated β-catenin/c-Myc pathway activation
- Potential biomarker for predicting postoperative prognosis and recurrence risk in ESCC
Summary
This comprehensive study investigated the role of Phosphoglycerate kinase 1 (PGK1) in esophageal squamous cell carcinoma (ESCC), revealing critical insights into tumor progression and potential therapeutic targeting. Through extensive molecular and clinical analyses, researchers demonstrated that elevated PGK1 levels are strongly associated with poor patient survival, advanced tumor characteristics, and increased metastatic potential.
The research uncovered a complex molecular mechanism where PGK1 interacts with myosin-9 (MYH9) to activate the β-catenin/c-Myc signaling pathway, particularly under hypoxic conditions. By facilitating MYH9-mediated ubiquitination and degradation of GSK-3β, PGK1 promotes tumor stemness, epithelial-mesenchymal transition (EMT), and enhanced migratory capacity of ESCC cells. These findings suggest PGK1 as a potential prognostic biomarker and therapeutic target for improving ESCC patient outcomes.