ArticleInternational journal of biological sciences2019
Activation of AMPK by metformin promotes renal cancer cell proliferation under glucose deprivation through its interaction with PKM2.
Article in International journal of biological sciences, 2019. 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, 56 citations in OpenAlex.
- Drug repurposing as a promising therapeutic strategy against renal cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- Targeting Pyruvate Kinase M2: Signal Transduction Pathways and Exploration of Cancer Therapeutic Strategies.The AAPS journal · 2026Review
- PRKAB2 as a tumor suppressor in renal cell carcinoma: inhibiting mitophagy via the LRPPRC-PRKN/parkin interaction and cardiolipin biosynthesis.Autophagy · 2026Article
- Identification of glycolysis-related molecular subtypes and prognostic model in intrahepatic cholangiocarcinoma.Discover oncology · 2025Article
- Nuclear PKM2: a signal receiver, a gene programmer, and a metabolic modulator.Journal of biomedical science · 2025Review
- Dissecting the role of metformin in urogenital malignancies.Annals of medicine and surgery (2012) · 2025Article
- PKM2 modulates chemotherapy sensitivity by regulating autophagy and predicts the prognosis and immunity in pancancer.Scientific reports · 2025Article
- Energy metabolism in health and diseases.Signal transduction and targeted therapy · 2025Review
- The regulatory roles and clinical significance of glycolysis in tumor.Cancer communications (London, England) · 2024Review
- Targeting glycolysis: exploring a new frontier in glioblastoma therapy.Frontiers in immunology · 2024Review
- Article
- GTF2E2 downregulated by miR-340-5p inhibits the malignant progression of glioblastoma.Cancer gene therapy · 2023Article
- The impact of cellular environment onFuture science OA · 2023Review
- The Effect of Different Glucose Concentrations on the Antiproliferative Activity of Metformin in MCF-7 Breast Cancer Cells.Pharmaceutics · 2023Article
- Review
- Artesunate targets cellular metabolism to regulate the Th17/Treg cell balance.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
- Research progress on the therapeutic effect and mechanism of metformin for lung cancer (Review).Oncology reports · 2023Review
- Targeting Glucose Metabolism Enzymes in Cancer Treatment: Current and Emerging Strategies.Cancers · 2022Review
- Metformin resistant MDA-MB-468 cells exhibit EMT-like phenotype and increased migration capacity.Molecular biology reports · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin, a common therapeutics for type 2 diabetics, was recently demonstrated to possess antitumor activity in various cancer types. However, its therapy effect in renal cell carcinoma (RCC) still remains controversial. In this study, we found that metformin treatment in RCC cells lead to activation of AMPK, which suppressed the cell proliferation under normal condition, but enhanced cell proliferation under glucose deprivation (GD) condition. Depletion of AMPK by siRNA abolished the proliferation effect of MF under GD condition. Mechanistic investigations revealed that the effect of AMPK on cell proliferation under GD condition is dependent on its nuclear translocation. Moreover, the nuclear AMPK recruits PKM2 and β-Catenin to form a complex, which promotes the transcription of cell proliferation related genes, including CCND1 and c-Myc. Furthermore, depletion of PKM2 or β-Catenin abrogated the proliferative effects of metformin under GD condition. And inhibition of PKM2 also re-sensitized the A498 xenograft in response to metformin treatment. Together, our results suggested that combined of AMPK activation and PKM2 depletion or inhibition can achieve better therapeutic effect for RCC patients.
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