ArticleNature communications2018
The critical role of AMPK in driving Akt activation under stress, tumorigenesis and drug resistance.
Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 2 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 2 syntheses or guidelines pooled it, 183 citations in OpenAlex.
- Neuroprotection through adiponectin receptor agonist: an updated meta-analysis of preclinical Alzheimer's disease studies.BMC neurology · 2025Pooled it
- Phytochemicals regulate cancer metabolism through modulation of the AMPK/PGC-1α signaling pathway.BMC cancer · 2024Pooled it
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Article
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- CHI3L1: a novel regulator of vascular remodeling in pulmonary arterial hypertension.Molecular and cellular biochemistry · 2026Article
- Connexin Regulation and Modulation of Neural Stem Cell Differentiation Induced by Cell-Permeable Itaconate.Journal of cellular physiology · 2026Article
- Adaptive Regulation of mTOR Activity by AMPK, Akt, and ATF6 Pathways in Pi*Z Alpha-1 Antitrypsin Deficient Hepatocytes.Biomolecules · 2026Article
- Transcriptional control of PPP2CB by YAP1 and TEAD1 mediates AMPK inhibition and mTORC1 activation in vascular smooth muscle cells.iScience · 2026Article
- Mevalonate pathway in pancreatic ductal adenocarcinoma: Mechanisms driving metabolic and cellular plasticity.Cancer pathogenesis and therapy · 2026Review
- Intricacies of PKB/Akt Activity after Sciatic Nerve Damage: A Comprehensive Review.Current protein & peptide science · 2026Review
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- EDIL3 alleviates Mannan-induced psoriatic arthritis by slowing the intracellular glycolysis process in mononuclear-derived dendritic cells.Inflammation · 2025Article
- Mechanistic Insights into Autophagy-Dependent Cell Death (ADCD): A Novel Avenue for Cancer Therapy.Cells · 2025Review
- Can vildagliptin protect against radiation-induced premature ovarian failure? Insights into the AMPK and AKT signaling pathways.BMC pharmacology & toxicology · 2025Article
- Long-Term Administration of Antioxidant N-Acetyl-L-Cysteine Impacts Beta Cell Oxidative Stress, Insulin Secretion, and Intracellular Signaling Pathways in Aging Mice.Antioxidants (Basel, Switzerland) · 2025Article
- Fructose induces inflammatory activation in macrophages and microglia through the nutrient-sensing ghrelin receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Mitigating ibrutinib-induced ventricular arrhythmia and cardiac dysfunction with metformin.Cancer innovation · 2025Article
- Rat Sarcoma Virus Family Genes in Acute Myeloid Leukemia: Pathogenetic and Clinical Implications.Biomedicines · 2025Review
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 3 countries.
Funding
Abstract
PI3K/Akt signaling is activated in cancers and governs tumor initiation and progression, but how Akt is activated under diverse stresses is poorly understood. Here we identify AMPK as an essential regulator for Akt activation by various stresses. Surprisingly, AMPK is also activated by growth factor EGF through Ca2+/Calmodulin-dependent kinase and is essential for EGF-mediated Akt activation and biological functions. AMPK phosphorylates Skp2 at S256 and promotes the integrity and E3 ligase activity of Skp2 SCF complex leading to K63-linked ubiquitination and activation of Akt and subsequent oncogenic processes. Importantly, AMPK-mediated Skp2 S256 phosphorylation promotes breast cancer progression in mouse tumor models, correlates with Akt and AMPK activation in breast cancer patients, and predicts poor survival outcomes. Finally, targeting AMPK-mediated Skp2 S256 phosphorylation sensitizes cells to anti-EGF receptor targeted therapy. Our study sheds light on how stress and EGF induce Akt activation and new mechanisms for AMPK-mediated oncogenesis and drug resistance.
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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.