ArticleThe Journal of clinical investigation2020
Gut epithelial TSC1/mTOR controls RIPK3-dependent necroptosis in intestinal inflammation and cancer.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
132 citing papers in PubMed, 1 synthesis or guideline pooled it, 202 citations in OpenAlex.
- Cullin Deneddylation Suppresses the Necroptotic Pathway in Cardiomyocytes.Frontiers in physiology · 2021Pooled it
- Crosstalk between circRNAs and the classic signaling pathways in IBD.RNA biology · 2026Review
- AMPK as a central regulator of necroptosis: mechanistic insights and therapeutic implications.Journal of physiology and biochemistry · 2026Review
- Non-canonical role of "S6K1-SGK1" pathway in neuronal necroptosis following traumatic brain injury.Genes & diseases · 2026Article
- Toxicarioside H induces cytoprotective autophagy by hindering the progression of necroptosis in triple-negative breast cancer cells.Translational oncology · 2026Article
- Microbiota in cancer: current understandings and future perspectives.Signal transduction and targeted therapy · 2026Review
- Analysis of Necroptosis-Related Genes and Immune Cell Infiltration in Infantile Hemangioma.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Adsorption-mediated modulation of lipopolysaccharide bioactivity by clinoptilolite zeolite withFrontiers in immunology · 2026Article
- Serum immune profiling suggests overlap between IBD patients with joint complaints and patients with spondyloarthritis.Frontiers in immunology · 2026Article
- Intestinal amino acid metabolic response and its roles in inflammatory bowel disease.Cell communication and signaling : CCS · 2025Review
- Integrated transcriptomic and microbiota analyses reveal growth-related intestinal responses to feeding strategies in Nibea coibor.Advanced biotechnology · 2025Article
- NUFIP1 at the crossroads of ribophagy and disease: unveiling therapeutic implications.Journal of translational medicine · 2025Review
- Exploratory study on the role of Clonorchis sinensis infection in promoting cholangiocarcinoma progression.Parasites & vectors · 2025Article
- Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy-related injury.Signal transduction and targeted therapy · 2025Article
- RIPK3 promotes skin inflammation by enhancing IL-36α signaling and necroptosis in keratinocytes.Cell death & disease · 2025Article
- The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.Nature communications · 2025Article
- DJ-1 counteracts Caveolin-1-mediated necroptosis to inhibit epithelial barrier dysfunction in colitis.Cell death & disease · 2025Article
- Interplay between NETosis and the lncRNA-microRNA regulatory axis in the immunopathogenesis of cancer.Journal of physiology and biochemistry · 2025Review
- TSC2-mutated perivascular epithelioid cell tumor with partial response to mTOR inhibition: a case report and literature review.Discover oncology · 2025Article
- The role and mechanism of TSC in kidney diseases: a literature review.BMC nephrology · 2025Review
72 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
Abstract
Although Western diet and dysbiosis are the most prominent environmental factors associated with inflammatory bowel diseases (IBDs), the corresponding host factors and cellular mechanisms remain poorly defined. Here we report that the TSC1/mTOR pathway in the gut epithelium represents a metabolic and innate immune checkpoint for intestinal dysfunction and inflammation. mTOR hyperactivation triggered by Western diet or Tsc1 ablation led to epithelium necroptosis, barrier disruption, and predisposition to dextran sulfate sodium-induced colitis and inflammation-associated colon cancer. Mechanistically, our results uncovered a critical role for TSC1/mTOR in restraining the expression and activation of RIPK3 in the gut epithelium through TRIM11-mediated ubiquitination and autophagy-dependent degradation. Notably, microbiota depletion by antibiotics or gnotobiotics attenuated RIPK3 expression and activation, thereby alleviating epithelial necroptosis and colitis driven by mTOR hyperactivation. mTOR primarily impinged on RIPK3 to potentiate necroptosis induced by TNF and by microbial pathogen-associated molecular patterns (PAMPs), and hyperactive mTOR and aberrant necroptosis were intertwined in human IBDs. Together, our data reveal a previously unsuspected link between the Western diet, microbiota, and necroptosis and identify the mTOR/RIPK3/necroptosis axis as a driving force for intestinal inflammation and 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.