ArticleMolecular cancer2015
PKM2 regulates neural invasion of and predicts poor prognosis for human hilar cholangiocarcinoma.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 2 of them syntheses that pooled it.
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Who cites it
47 citing papers in PubMed, 2 syntheses or guidelines pooled it, 75 citations in OpenAlex.
- Prognostic role of glycolysis for cancer outcome: evidence from 86 studies.Journal of cancer research and clinical oncology · 2019Pooled it
- Pyruvate kinase M2 (PKM2) expression correlates with prognosis in solid cancers: a meta-analysis.Oncotarget · 2017Pooled it
- Clinicopathological and prognostic significance of PKM2 protein expression in cirrhotic hepatocellular carcinoma and non-cirrhotic hepatocellular carcinoma.Scientific reports · 2017Trial
- Integrated Transcriptomic Analysis and Functional Validation Identify CNTN1 as a Novel Metastatic Driver in Hilar Cholangiocarcinoma.Biomedicines · 2026Article
- Beyond the convergence of metabolic reprogramming in primary liver cancer: a comprehensive review on energy and lipids metabolism.Frontiers in cell and developmental biology · 2026Review
- Metabolic reprogramming in hepatocellular carcinoma: mechanisms and therapeutic implications.Experimental & molecular medicine · 2025Review
- Advances in the Use of Metformin for Liver Disease.Current medicinal chemistry · 2025Review
- USP28 promotes tumor progression and glycolysis by stabilizing PKM2/Hif1-α in cholangiocarcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Metformin dampens the progression of cholangiofibrosis induced by thioacetamide using deep learning.Heliyon · 2024Article
- Personalized treatment of perihilar cholangiocarcinoma based on tumor genetic and molecular characteristics.World journal of gastrointestinal surgery · 2024Article
- UBE2M forms a positive feedback loop with estrogen receptor to drive breast cancer progression and drug resistance.Cell death & disease · 2024Article
- Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis.Digestive diseases and sciences · 2024Article
- Recent Advances on PKM2 Inhibitors and Activators in Cancer Applications.Current medicinal chemistry · 2024Review
- Targeting Glycolytic Reprogramming in Cholangiocarcinoma: A Novel Approach for Metabolic Therapy.Journal of inflammation research · 2024Review
- Pyruvate kinase M2 (PKM-2) expression and prognostic significance in glioblastoma patients.Journal of neuro-oncology · 2023Article
- Glycolysis in Chronic Liver Diseases: Mechanistic Insights and Therapeutic Opportunities.Cells · 2023Review
- The clinical implications and molecular features of intrahepatic cholangiocarcinoma with perineural invasion.Hepatology international · 2023Article
- Application and development of Deuterium Metabolic Imaging in tumor glucose metabolism: visualization of different metabolic pathways.Frontiers in oncology · 2023Review
- Phytochemicals targeting glycolysis in colorectal cancer therapy: effects and mechanisms of action.Frontiers in pharmacology · 2023Review
- Lactate receptor HCAR1 regulates cell growth, metastasis and maintenance of cancer‑specific energy metabolism in breast cancer cells.Molecular medicine reports · 2022Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe therapeutic and prognostic value of the glycolytic enzymes hexokinase, phosphofructokinase, and pyruvate kinase (PK) has been implicated in a variety of cancers, while their roles in treatment of and prognosis for hilar cholangiocarcinoma (HC) remain unclear. In this study, we determined the expression of PKM2 in and its impact on biology and clinical outcome of human HC.
methodsThe regulation and function of PKM2 in HC pathogenesis was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival.
resultsWe found that expression of hexokinase 1 and the M2 splice isoform of PK (PKM2) was upregulated in HC tissues and that this expression correlated with tumor recurrence and outcome. PKM2 expression was increased in HC cases with chronic cholangitis as demonstrated by isobaric tags for relative and absolute quantification. High PKM2 expression was highly correlated with high syndecan 2 (SDC2) expression and neural invasion. PKM2 downregulation led to a decrease in SDC2 expression. Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth.
conclusionsPKM2 regulates neural invasion of HC cells at least in part via regulation of SDC2. Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC. Therefore, PKM2 is an independent prognostic factor and potential therapeutic target for human HC.
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