Evidence map›Paper›PMID 40534132›Full record

ArticleClinical and translational medicine2025

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

Jia-Cheng Xu, Lin-Feng Wu, Tian-Yin Chen, Yan-Bo Liu, Yi-Fei Zhang, Ping-Hong Zhou, Yi-Qun Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jia-Cheng XuDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Lin-Feng WuDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Tian-Yin ChenDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Yan-Bo LiuDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Yi-Fei ZhangDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Ping-Hong ZhouDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-5434-0540
Yi-Qun ZhangDepartment of Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.ORCID 0000-0002-0822-6384

Funding

National Natural Science Foundation of China 82172787Shanghai Engineering and Research Center of Diagnostic and Therapeutic Endoscopy 16DZ2280900
6 · The paper itself

Abstract

backgroundPhosphoglycerate 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.

methodsEsophageal 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.

resultsWe 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 increasing c-Myc expression. In addition, we found that hypoxic conditions upregulated PGK1, with HIF-1α transactivating PGK1 expression, further promoting the PGK1-MYH9 interaction and PGK1/MYH9/β-catenin/c-Myc axis activation.

conclusionsPGK1 promotes ESCC tumourigenicity and migratory capacity by facilitating β-catenin-dependent c-Myc transcription. Under hypoxic conditions, the PGK1‒MYH9 interaction is strengthened, and HIF-1α-mediated transcription increases PGK1 expression, thereby activating the β-catenin/c-Myc signalling pathway. Taken together, PGK1 holds promise as a potential biomarker for predicting postoperative prognosis and recurrence in patients with ESCC.

Indexed as

beta CateninEsophageal NeoplasmsEsophageal Squamous Cell CarcinomaGlycogen Synthase Kinase 3 betaMyosin Heavy ChainsPhosphoglycerate KinaseAnimalsCell Line, TumorDisease ProgressionFemaleHumansMaleMiceSignal Transductionbeta CateninCTNNB1 protein, humanGlycogen Synthase Kinase 3 betaGSK3B protein, humanMYH9 protein, humanMyosin Heavy ChainsPGK1 protein, humanPhosphoglycerate Kinaseesophageal squamous cell carcinomahypoxiaMYH9PGK1β‐catenin signalling pathway

Identifiers

PMID40534132
PMCPMC12177104

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.