ArticleCell2016
An Ancient, Unified Mechanism for Metformin Growth Inhibition in C. elegans and Cancer.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 papers, 3 of them syntheses that pooled it.
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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Who cites it
143 citing papers in PubMed, 3 syntheses or guidelines pooled it, 225 citations in OpenAlex.
- Association of metformin use and cancer incidence: a systematic review and meta-analysis.Journal of the National Cancer Institute · 2024 · on this mapPooled it
- Pooled it
- Metformin is associated with survival benefit in pancreatic cancer patients with diabetes: a systematic review and meta-analysis.Oncotarget · 2017 · on this mapPooled it
- p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans.GeroScience · 2026Article
- 5-Fluorouracil-based chemotherapy disrupts autophagy flux and protein synthesis in cultured myotubes: a role for mTORC1 signaling.American journal of physiology. Cell physiology · 2026Article
- ACAD10 encodes two orphan enzymes in the ether lipid biosynthetic and salvage pathways.bioRxiv : the preprint server for biology · 2026Article
- Developmental priming of adult proteostasis and longevity by NuA4 complex activity in early life.The EMBO journal · 2026Article
- A lipid-sensitive food choice behavior influences aging outcomes from a longevity-promoting diet.The FEBS journal · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Paternal preconceptional metformin exposure induces metabolic dysregulation in offspring.Cell discovery · 2026Article
- Hormetic fasting extends Caenorhabditis elegans lifespan via H3K27 acetylation of lipid catabolism and antioxidant genes.Cell reports · 2026Article
- Dendrobium officinale leaf extract extends the mean lifespan in Caenorhabditis elegans via the DAF-16/SOD-3 axis.Biogerontology · 2026Article
- Metformin in Diabetes and Beyond: Therapeutic Mechanisms, Lactic Acidosis, Organ-Specific Effects, and Nanotechnology-Based Delivery Strategies.Current medical science · 2026Review
- Organellar insights in ageing and longevity.Nature cell biology · 2026Review
- Immune regulators PALS-25 and PALS-22 localize to mitochondria and regulate mitochondrial fragmentation iniScience · 2026Article
- From Metabolism to Longevity: Molecular Mechanisms Underlying Metformin's Anticancer and Anti-Aging Effects.Current issues in molecular biology · 2026Review
- Mitochondrial superoxide regulates nuclear envelope integrity and ageing via redox-mediated lipid metabolism.Nature metabolism · 2026Article
- Multilayered regulation of longevity in Caenorhabditis elegans.Molecules and cells · 2026Review
- Metabolic-inhibitor profiling links phenotype and transcriptome ofFood chemistry. Molecular sciences · 2025Article
- Hormetic nutrient stress promotes longevity by orchestrating histone acetylation on key lipid catabolism and antioxidant defense genes.bioRxiv : the preprint server for biology · 2025Article
83 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Metformin has utility in cancer prevention and treatment, though the mechanisms for these effects remain elusive. Through genetic screening in C. elegans, we uncover two metformin response elements: the nuclear pore complex (NPC) and acyl-CoA dehydrogenase family member-10 (ACAD10). We demonstrate that biguanides inhibit growth by inhibiting mitochondrial respiratory capacity, which restrains transit of the RagA-RagC GTPase heterodimer through the NPC. Nuclear exclusion renders RagC incapable of gaining the GDP-bound state necessary to stimulate mTORC1. Biguanide-induced inactivation of mTORC1 subsequently inhibits growth through transcriptional induction of ACAD10. This ancient metformin response pathway is conserved from worms to humans. Both restricted nuclear pore transit and upregulation of ACAD10 are required for biguanides to reduce viability in melanoma and pancreatic cancer cells, and to extend C. elegans lifespan. This pathway provides a unified mechanism by which metformin kills cancer cells and extends lifespan, and illuminates potential cancer targets. PAPERCLIP.
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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.