ArticleThe Journal of clinical investigation2017
Kinase-independent functions of RIPK1 regulate hepatocyte survival and liver carcinogenesis.
Article in The Journal of clinical investigation, 2017. 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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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
21 citing papers in PubMed, 32 citations in OpenAlex.
- Modulation of Inflammation-Driven Hepatocarcinogenesis: The Hepatic Immune Microenvironment, Gut-Liver Axis, and Neuroregulation.Journal of hepatocellular carcinoma · 2026Review
- Targeting the Cdc2-like kinase 2 for overcoming platinum resistance in ovarian cancer.MedComm · 2024Article
- Mediators of necroptosis: from cell death to metabolic regulation.EMBO molecular medicine · 2024Review
- Receptor-interacting protein kinase-1 ablation in liver parenchymal cells promotes liver fibrosis in murine NASH without affecting other symptoms.Journal of molecular medicine (Berlin, Germany) · 2022Article
- RIPK1 in Liver Parenchymal Cells Limits Murine Hepatitis during Acute CClInternational journal of molecular sciences · 2022Article
- Necroptosis-driving genesJournal for immunotherapy of cancer · 2022Article
- RIP1 kinase activity promotes steatohepatitis through mediating cell death and inflammation in macrophages.Cell death and differentiation · 2021Article
- Review
- Receptor-interacting protein in malignant digestive neoplasms.Journal of Cancer · 2021Review
- microRNA-199a-3p inhibits hepatic apoptosis and hepatocarcinogenesis by targeting PDCD4.Oncogenesis · 2020Article
- Multitasking Kinase RIPK1 Regulates Cell Death and Inflammation.Cold Spring Harbor perspectives in biology · 2020Review
- Protective Properties of FOXO1 Inhibition in a Murine Model of Non-alcoholic Fatty Liver Disease Are Associated With Attenuation of ER Stress and Necroptosis.Frontiers in physiology · 2020Article
- RIPK1 and death receptor signaling drive biliary damage and early liver tumorigenesis in mice with chronic hepatobiliary injury.Cell death and differentiation · 2019Article
- Necroptosis regulates tumor repopulation after radiotherapy via RIP1/RIP3/MLKL/JNK/IL8 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease.Physiological reviews · 2019Review
- C-Phycocyanin Suppresses the In Vitro Proliferation and Migration of Non-Small-Cell Lung Cancer Cells through Reduction of RIPK1/NF-κB Activity.Marine drugs · 2019Article
- Depletion of RIPK1 in hepatocytes exacerbates liver damage in fulminant viral hepatitis.Cell death & disease · 2019Article
- Rethink of EGFR in Cancer With Its Kinase Independent Function on Board.Frontiers in oncology · 2019Article
- Review
- Deficiency of pyruvate dehydrogenase kinase 4 sensitizes mouse liver to diethylnitrosamine and arsenic toxicity through inducing apoptosis.Liver research (Beijing, China) · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The mechanisms that regulate cell death and inflammation play an important role in liver disease and cancer. Receptor-interacting protein kinase 1 (RIPK1) induces apoptosis and necroptosis via kinase-dependent mechanisms and exhibits kinase-independent prosurvival and proinflammatory functions. Here, we have used genetic mouse models to study the role of RIPK1 in liver homeostasis, injury, and cancer. While ablating either RIPK1 or RelA in liver parenchymal cells (LPCs) did not cause spontaneous liver pathology, mice with combined deficiency of RIPK1 and RelA in LPCs showed increased hepatocyte apoptosis and developed spontaneous chronic liver disease and cancer that were independent of TNF receptor 1 (TNFR1) signaling. In contrast, mice with LPC-specific knockout of Ripk1 showed reduced diethylnitrosamine-induced (DEN-induced) liver tumorigenesis that correlated with increased DEN-induced hepatocyte apoptosis. Lack of RIPK1 kinase activity did not inhibit DEN-induced liver tumor formation, showing that kinase-independent functions of RIPK1 promote DEN-induced hepatocarcinogenesis. Moreover, mice lacking both RIPK1 and TNFR1 in LPCs displayed normal tumor formation in response to DEN, demonstrating that RIPK1 deficiency decreases DEN-induced liver tumor formation in a TNFR1-dependent manner. Therefore, these findings indicate that RIPK1 cooperates with NF-κB signaling to prevent TNFR1-independent hepatocyte apoptosis and the development of chronic liver disease and cancer, but acts downstream of TNFR1 signaling to promote DEN-induced liver tumorigenesis.
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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.