ArticleMolecular pharmacology2015
AMPK Inhibits the Stimulatory Effects of TGF-β on Smad2/3 Activity, Cell Migration, and Epithelial-to-Mesenchymal Transition.
Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 94 citations in OpenAlex.
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- Combined Therapy with Pirfenidone, Metformin, and Mesenchymal Stem Cells Attenuates Bleomycin-Induced Pulmonary Fibrosis in Rats.Biomedicines · 2026Article
- FNDC5/Irisin Attenuates TGF-β-induced Fibroblast Differentiation Via AMPK/Nrf2 Signaling and Mitochondrial Stabilization in Subepithelial Fibrosis.Inflammation · 2026Article
- TGF-beta inhibitors in cancer therapy: a review of the TGF-beta signal transduction pathway and current developments.EXCLI journal · 2026Review
- The mechanistic role of adipokine imbalance in airway inflammation, hyperresponsiveness, and remodeling in obesity-related asthma.Frontiers in endocrinology · 2026Review
- Dapagliflozin inhibits TGF-β-induced transdifferentiation of valvular interstitial cells and mitral valvular degeneration.Journal of molecular medicine (Berlin, Germany) · 2025Article
- CRCs-CAFs crosstalk-targeted nano-delivery system reprograms tumor microenvironment for oxaliplatin resistance reversing and liver metastasis inhibition in colorectal cancer.Bioactive materials · 2025Article
- Escape from TGF-β-induced senescence promotes aggressive hallmarks in epithelial hepatocellular carcinoma cells.Molecular oncology · 2025Article
- The molecular determinants regulating redox signaling in diabetic endothelial cells.Frontiers in pharmacology · 2025Review
- Application of SGLT-2 inhibitors in non-diabetic CKD: mechanisms, efficacy, and safety.Frontiers in medicine · 2025Review
- Striking Cardioprotective Effects of an Adiponectin Receptor Agonist in an Aged Mouse Model of Duchenne Muscular Dystrophy.Antioxidants (Basel, Switzerland) · 2024Article
- The metabolic sensor AMPK: Twelve enzymes in one.Molecular metabolism · 2024Review
- Progress in antitumor mechanisms and applications of phenformin (Review).Oncology reports · 2024Review
- Aerobic exercise suppresses CCN2 secretion from senescent muscle stem cells and boosts muscle regeneration in aged mice.Journal of cachexia, sarcopenia and muscle · 2024Article
- Statins in Mitigating Anticancer Treatment-Related Cardiovascular Disease.International journal of molecular sciences · 2024Review
- Genetic variation at a splicing branch point in intron 7 of STK11: a rare variant decreasing its expression in a Chinese family with Peutz-Jeghers syndrome.World journal of surgical oncology · 2024Article
- AMPK signaling inhibits the differentiation of myofibroblasts: impact on age-related tissue fibrosis and degeneration.Biogerontology · 2024Review
- Skeletal muscle-specific inducible AMPKα1/α2 knockout mice develop muscle weakness, glycogen depletion, and fibrosis that persists during disuse atrophy.American journal of physiology. Endocrinology and metabolism · 2024Article
- Oxoglaucine Suppresses Hepatic Fibrosis by Inhibiting TGFβ-Induced Smad2 Phosphorylation and ROS Generation.Molecules (Basel, Switzerland) · 2023Article
- AMP-activated protein kinase inhibition in fibro-adipogenic progenitors impairs muscle regeneration and increases fibrosis.Journal of cachexia, sarcopenia and muscle · 2023Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
AMP-activated protein kinase (AMPK), an important downstream effector of the tumor suppressor liver kinase 1 (LKB1) and pharmacologic target of metformin, is well known to exert a preventive and inhibitory effect on tumorigenesis; however, its role in cancer progression and metastasis has not been well characterized. The present study investigates the potential roles of AMPK in inhibiting cancer-cell migration and epithelial-to-mesenchymal transition (EMT) by regulating the canonical transforming growth factor β (TGF-β) signaling pathway, an important promoting factor for cancer progression. Our results showed that activation of AMPK by metformin inhibited TGF-β-induced Smad2/3 phosphorylation in cancer cells in a dose-dependent manner. The effect of metformin is dependent on the presence of LKB1. A similar effect was obtained by expressing a constitutive active mutant of AMPKα1 subunit, whereas the expression of a dominant negative mutant of AMPKα1 or ablation of AMPKα subunits greatly enhanced TGF-β stimulation of Smad2/3 phosphorylation. As a consequence, expression of genes downstream of Smad2/3, including plasminogen activator inhibitor-1, fibronectin, and connective tissue growth factor, was suppressed by metformin in a LKB1-dependent fashion. In addition, metformin blocked TGF-β-induced inteleukin-6 expression through both LKB1-dependent and -independent mechanisms. Our results also indicate that activation of LKB1/AMPK inhibits TGF-β-stimulated cancer cell migration. Finally, TGF-β induction of EMT was inhibited by phenformin and enhanced by knockdown of LKB1 expression with shRNA. Together, our data suggest that AMPK could be a drug target for controlling cancer progression and metastasis.
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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.