Hypoxia‐induced PGK1 expression promotes esophageal squamous cell carcinoma progression via stimulating MYH9‐mediated GSK3β/β‐catenin signalling

作者：Junyan Xu, Linfeng Wu, Tian‐yin Chen, Yan‐Bo Liu, Yifei Zhang, Yi‐fei Zhang, Ping‐Hong Zhou, Yiqun Zhang, Yiqun Zhang · 发表于：Clinical and Translational Medicine · 年份：2025 · DOI：10.1002/ctm2.70376 · 被引用次数：5 · 研究领域：Cancer, Hypoxia, and Metabolism、Glycosylation and Glycoproteins Research、Wnt/β-catenin signaling in development and cancer

BACKGROUND: Phosphoglycerate kinase 1 (PGK1) serves as a critical metabolic enzyme in the process of glycolysis and has many nonmetabolic functions in tumour progression. One of the most prevalent malignant tumours is still esophageal squamous cell carcinoma (ESCC), with high recurrence rates, high probabilities of metastasis, and poor prognoses. However, the molecular mechanisms and physiological contribution of PGK1 to ESCC carcinogenesis remain largely elusive. METHODS: Esophageal cancer bioinformatics analysis and tissue microarray analysis were employed to elucidate the aberrant expression of PGK1 during ESCC progression. The carcinogenic effect of PGK1 was examined using cell proliferation, migration and sphere formation assays. Mass spectrometry analysis, immunoprecipitation, ChIP and luciferase assays, hypoxia assays and in vitro and in vivo experiments were used to clarify the mechanism of the PGK1‒MYH9 interaction in the β-catenin/c-Myc signalling pathway. RESULTS: We clarified that in patients with ESCC, elevated PGK1 levels were linked to poor survival, tumour size, lymph node metastatic status, and TNM stage. In vivo and in vitro experimental analyses revealed that PGK1 promoted ESCC cell tumour stemness and EMT both in vivo and in vitro. Mechanistically, we discovered that PGK1 interacts with myosin-9 (MYH9), leading to MYH9-mediated ubiquitination-mediated degradation of GSK-3β, thereby triggering the β-catenin signalling pathway and transcriptionally increasin...