ArticleCells2020
Metformin Inhibits Tumor Metastasis through Suppressing Hsp90α Secretion in an AMPKα1-PKCγ Dependent Manner.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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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.
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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.
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Who cites it
16 citing papers in PubMed, 19 citations in OpenAlex.
- Extracellular Hsp90α Promotes Tumor Lymphangiogenesis and Lymph Node Metastasis in Breast Cancer.International journal of molecular sciences · 2021Trial
- Potential of HSP90AA1 as Diagnostic, Prognostic, and Immunological Biomarkers in Human Cancer Demonstrated through Pan-Cancer Investigation: A Bioinformatics Analysis.Current medicinal chemistry · 2026Article
- β-Mangostin Attenuates TET2-Mediated DNA Demethylation of Prkcg in the Prevention of Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Role of eHsp90 in Extracellular Matrix Remodeling, Tumor Invasiveness, and Metastasis.Cancers · 2024Review
- Article
- Diosgenin derivative ML5 attenuates MPTP-induced neuronal impairment via regulating AMPK/PGC-1α-mediated mitochondrial biogenesis and fusion/fission.American journal of translational research · 2024Article
- Repurposing Metformin for the Treatment of Atrial Fibrillation: Current Insights.Vascular health and risk management · 2024Review
- Targeted Inhibition of Hsp90 in Combination with Metformin Modulates Programmed Cell Death Pathways in A549 Lung Cancer Cells.Applied biochemistry and biotechnology · 2023Article
- Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.Cancers · 2023Article
- Saccharomyces cerevisiae as a tool for deciphering Hsp90 molecular chaperone function.Essays in biochemistry · 2023Article
- New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.International journal of molecular sciences · 2021Review
- Additive Antiproliferative and Antiangiogenic Effects of Metformin and Pemetrexed in a Non-Small-Cell Lung Cancer Xenograft Model.Frontiers in cell and developmental biology · 2021Article
- Plasmatic Levels of HSP90α at Diagnosis: A Novel Prognostic Indicator of Clinical Outcome in Advanced Lung Cancer Patients Treated With PD-1/PD-L1 Inhibitors Plus Chemotherapy.Frontiers in oncology · 2021Article
- Trametenolic Acid B Triggers HSP90AA4P and Autophagy in HepG2/2.2.15 Cells by Proteomic Analysis.ACS omega · 2020Article
- Review
- Mechanisms of metformin inhibiting cancer invasion and migration.American journal of translational research · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metformin has been documented in epidemiological studies to mitigate tumor progression. Previous reports show that metformin inhibits tumor migration in several cell lines, such as MCF-7 and H1299, but the mechanisms whereby metformin exerts its inhibitory effects on tumor metastasis remain largely unknown. The secreted proteins in cancer cell-derived secretome have been reported to play important roles in tumor metastasis, but whether metformin has an effect on tumor secretome remains unclear. Here we show that metformin inhibits tumor metastasis by suppressing Hsp90α (heat shock protein 90α) secretion. Mass spectrometry (MS) analysis and functional validation identify that eHsp90α (extracellular Hsp90α) is one of the most important secreted proteins for metformin to inhibit tumor cells migration, invasion and metastasis both in vitro and in vivo. Moreover, we find that metformin inhibits Hsp90α secretion in an AMPKα1 dependent manner. Our data elucidate that AMPKα1 (AMP-activated protein kinase α1) decreases the phosphorylation level of Hsp90α by inhibiting the kinase activity of PKCγ (protein kinase Cγ), which suppresses the membrane translocation and secretion of Hsp90α. Collectively, our results illuminate that metformin inhibits tumor metastasis by suppressing Hsp90α secretion in an AMPKα1 dependent manner.
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Registered trials
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.