ArticleBMC cancer2021
Inhibition of mTORC1 through ATF4-induced REDD1 and Sestrin2 expression by Metformin.
Article in BMC cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 20 citations in OpenAlex.
- Phosphatidylinositol transfer protein-1 integrates insulin/IGF-1 and TOR signaling to negatively regulate lifespan and healthspan in Caenorhabditis elegans.Journal of biomedical science · 2026Article
- Review
- From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin's Anticancer and Anti-Aging Effects.Current issues in molecular biology · 2026Review
- From molecular damage to regulatory constraint: epigenetic and metabolic limits of cellular plasticity in aging.Frontiers in aging · 2026Review
- Beyond diabetes: harnessing the power of metformin in burn care.Critical care (London, England) · 2025Review
- The ATF4-glutamine axis: a central node in cancer metabolism, stress adaptation, and therapeutic targeting.Cell death discovery · 2025Review
- Review
- Targeting mTOR Kinase with Natural Compounds: Potent ATP-Competitive Inhibition Through Enhanced Binding Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Metformin: Beyond Type 2 Diabetes Mellitus.Cureus · 2024Review
- Metformin induces ZFP36 by mTORC1 inhibition in cervical cancer-derived cell lines.BMC cancer · 2024Article
- mTOR: Its Critical Role in Metabolic Diseases, Cancer, and the Aging Process.International journal of molecular sciences · 2024Review
- Phenformin activates ER stress to promote autophagic cell death via NIBAN1 and DDIT4 in oral squamous cell carcinoma independent of AMPK.International journal of oral science · 2024Article
- Sestrin2 can alleviate endoplasmic reticulum stress to improve traumatic brain injury by activating AMPK/mTORC1 signaling pathway.Metabolic brain disease · 2024Review
- Research Progress on the Use of Metformin in Leukemia Treatment.Current treatment options in oncology · 2024Review
- Glucose promotes cell growth and casein synthesis via ATF4/Nrf2-Sestrin2- AMPK-mTORC1 pathway in dairy cow mammary epithelial cells.Animal biotechnology · 2023Article
- Metformin promotes ferroptosis and sensitivity to sorafenib in hepatocellular carcinoma cells via ATF4/STAT3.Molecular biology reports · 2023Article
- A coordinated multiorgan metabolic response contributes to human mitochondrial myopathy.EMBO molecular medicine · 2023Article
- The development and benefits of metformin in various diseases.Frontiers of medicine · 2023Review
- Sensing of the non-essential amino acid tyrosine governs the response to protein restriction in Drosophila.Nature metabolism · 2022Article
- ER stress induces myocardial dysfunction and cardiac autophagy in Sestrin2 knockout mice.American journal of translational research · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the major anticancer effect of metformin involves AMPK-dependent or AMPK-independent mTORC1 inhibition, the mechanisms of action are still not fully understood.
methodsTo investigate the molecular mechanisms underlying the effect of metformin on the mTORC1 inhibition, MTT assay, RT-PCR, and western blot analysis were performed.
resultsMetformin induced the expression of ATF4, REDD1, and Sestrin2 concomitant with its inhibition of mTORC1 activity. Treatment with REDD1 or Sestrin2 siRNA reversed the mTORC1 inhibition induced by metformin, indicating that REDD1 and Sestrin2 are important for the inhibition of mTORC1 triggered by metformin treatment. Moreover, REDD1- and Sestrin2-mediated mTORC1 inhibition in response to metformin was independent of AMPK activation. Additionally, lapatinib enhances cell sensitivity to metformin, and knockdown of REDD1 and Sestrin2 decreased cell sensitivity to metformin and lapatinib.
conclusionsATF4-induced REDD1 and Sestrin2 expression in response to metformin plays an important role in mTORC1 inhibition independent of AMPK activation, and this signalling pathway could have therapeutic value.
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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.