ArticleCell death & disease2018
High PGAM5 expression induces chemoresistance by enhancing Bcl-xL-mediated anti-apoptotic signaling and predicts poor prognosis in hepatocellular carcinoma patients.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 48 citations in OpenAlex.
- ZO-2 blocks the localization of PGAM5 protein to the mitochondrial membrane and suppresses pancreatic cancer malignancy through metabolic reprogramming.Genes & diseases · 2027Article
- NCBP2 Regulates PGAM5-Mediated Mitophagy Via KIF23 Alternative Splicing To Promote Cervical Cancer ProgressionRun Title: NCBP2 Promotes Cervical Cancer Via Mitophagy.Applied biochemistry and biotechnology · 2026Article
- Article
- BCL-2 and BCL-xL in Cancer: Regulation, Function, and Therapeutic Targeting.International journal of molecular sciences · 2026Review
- LHPP expression in triple-negative breast cancer promotes tumor growth and metastasis by modulating the tumor microenvironment.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Alternative splicing: from tumorigenesis to neoantigen-mediated cancer immunotherapy.Biomarker research · 2025Review
- PGAM5 cleavage and oligomerization equilibrates mitochondrial dynamics under stress by regulating DRP1 function.Journal of cell science · 2025Article
- Article
- Review
- The dual role of PGAM5 in inflammation.Experimental & molecular medicine · 2025Review
- Disruption of tumor-intrinsic PGAM5 increases anti-PD-1 efficacy through the CCL2 signaling pathway.Journal for immunotherapy of cancer · 2025Article
- Establishment and Validation of the Novel Necroptosis-related Genes for Predicting Stemness and Immunity of Hepatocellular CarcinomaCombinatorial chemistry & high throughput screening · 2025Article
- M1 macrophage-derived exosomes alleviate leukemia by causing mitochondrial dysfunction.Annals of hematology · 2024Article
- Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence.Computational and structural biotechnology journal · 2024Article
- Mitoepigenetics pathways and natural compounds: a dual approach to combatting hepatocellular carcinoma.Medical oncology (Northwood, London, England) · 2024Review
- Ponicidin Promotes Hepatocellular Carcinoma Mitochondrial Apoptosis by Stabilizing Keap1-PGAM5 Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PJA1-mediated suppression of pyroptosis as a driver of docetaxel resistance in nasopharyngeal carcinoma.Nature communications · 2024Article
- A Review of the Potential Role of CoQ10 in the Treatment of Hepatocellular Carcinoma.Biochemical genetics · 2024Review
- Review
- A comprehensive analysis of the potential role of necroptosis in hepatocellular carcinoma using single-cell RNA Seq and bulk RNA Seq.Journal of cancer research and clinical oncology · 2023Article
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatocellular carcinoma (HCC) is the one of most common and deadly cancers, and is also highly resistant to conventional chemotherapy treatments. Mitochondrial phosphoglycerate mutase/protein phosphatase (PGAM5) regulates mitochondrial homeostasis and cell death, however, little is known about its roles in cancer. The aim of this study was to explore the clinical significance and potential biological functions of PGAM5 in hepatocellular carcinoma. For the first time, our results show that PGAM5 is significantly upregulated in HCC compared with corresponding adjacent noncancerous hepatic tissues and high PGAM5 expression is an independent predictor of reduced survival times in both univariate and multivariate analyses. Additionally, in vivo and in vitro studies showed that depleting PGAM5 expression inhibited tumor growth and increased the 5-fluorouracil sensitivity of HCC cells. Conversely, restoring PGAM5 expression in PGAM5-knockdown cells dramatically enhanced HCC cell resistance to 5-fluorouracil. Importantly, we demonstrated that the mechanism of 5-fluorouracil resistance conferred to HCC cells by PGAM5 was via inhibiting BAX- and cytochrome C-mediated apoptotic signaling by interacting and stabilizing Bcl-xL. Consistently, in the same cohorts of HCC patient tissues, Bcl-xL expression was positively correlated with PGAM5, and together predicted poor prognoses. In Conclusion, Our data highlight the molecular etiology and clinical significance of PGAM5 in HCC. Targeting the novel signaling pathway mediated by PGAM5/Bcl-xL may represent a new therapeutic strategy to improve the survival outcomes of HCC patients.
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