ArticleNature cancer2024
Blocking methionine catabolism induces senescence and confers vulnerability to GSK3 inhibition in liver cancer.
Article in Nature cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Global research trends and emerging themes in amino acid deprivation based cancer therapy: a bibliometric and visualization study.Frontiers in immunology · 2026Pooled it
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- LC-MS/MS-based clinical value exploration of the methionine cycle in luminal breast cancer.Oncology letters · 2026Article
- Integrating proteomics and metabolomics to reveal MAT2A for metabolic reprogramming in non-small cell lung cancer cells.iScience · 2026Article
- Nanozyme-Mediated Cellular and Microenvironmental Metabolic Reprogramming for Boosting Cancer Immunotherapy.Small (Weinheim an der Bergstrasse, Germany) · 2026Review
- The glycine N-methyltransferase amino-terminus regulates folate-dependent feedback inhibition and S-adenosylmethionine homeostasis.The Journal of biological chemistry · 2026Article
- SUMOylation activates ECHS1 for adaptive catabolism in lung cancer.Cell death & disease · 2026Article
- Role of methionine metabolism in cancer: recent advances in molecular mechanisms and therapeutic implications.Experimental hematology & oncology · 2026Review
- Metabolic remodeling by circular RNAs in gastric tumorigenesis: From mechanisms to biomarker discovery (Review).International journal of oncology · 2026Review
- Prolonged S-adenosylmethionine exposure is associated with poorer treatment response and adverse outcomes in breast cancer: a retrospective cohort study.World journal of surgical oncology · 2026Article
- Methionine restriction and mimetics to ameliorate human aging and disease.Trends in endocrinology and metabolism: TEM · 2026Review
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- The GNMT N-terminus Couples Folate Feedback to Methyl-donor Homeostasis.bioRxiv : the preprint server for biology · 2026Article
- [Construction of a methionine metabolism-related prognostic signature and the effect of targeting methionine metabolism on diffuse large B-cell lymphoma].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2026Article
- BRD2 upregulation as a pan-cancer adaptive resistance mechanism to BET inhibition.Cellular & molecular biology letters · 2026Article
- Nanozyme for precision treatment of hepatocellular carcinoma.Materials today. Bio · 2026Review
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- α-Ketoglutarate dictates AMPK protein synthesis for energy sensing in human cancers.Nature chemical biology · 2026Article
- Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.Signal transduction and targeted therapy · 2026Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Availability of the essential amino acid methionine affects cellular metabolism and growth, and dietary methionine restriction has been implicated as a cancer therapeutic strategy. Nevertheless, how liver cancer cells respond to methionine deprivation and underlying mechanisms remain unclear. Here we find that human liver cancer cells undergo irreversible cell cycle arrest upon methionine deprivation in vitro. Blocking methionine adenosyl transferase 2A (MAT2A)-dependent methionine catabolism induces cell cycle arrest and DNA damage in liver cancer cells, resulting in cellular senescence. A pharmacological screen further identified GSK3 inhibitors as senolytics that selectively kill MAT2A-inhibited senescent liver cancer cells. Importantly, combined treatment with MAT2A and GSK3 inhibitors therapeutically blunts liver tumor growth in vitro and in vivo across multiple models. Together, methionine catabolism is essential for liver tumor growth, and its inhibition can be exploited as an improved pro-senescence strategy for combination with senolytic agents to treat liver cancer.
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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.