ArticleJournal of experimental & clinical cancer research : CR2015
Tumor progression locus 2 ablation suppressed hepatocellular carcinoma development by inhibiting hepatic inflammation and steatosis in mice.
Article in Journal of experimental & clinical cancer research : CR, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- TPL2 Promotes Gastric Cancer Progression and Chemoresistance Through a Hypoxia-Induced Positive Feedback Loop with PPARδ.International journal of biological sciences · 2025Article
- Spontaneous Occurrence of Various Types of Hepatocellular Adenoma in the Livers of Metabolic Syndrome-Associated Steatohepatitis Model TSOD Mice.International journal of molecular sciences · 2022Article
- Review
- MAP3K8 Is a Prognostic Biomarker and Correlated With Immune Response in Glioma.Frontiers in molecular biosciences · 2021Article
- Effect of MAP3K8 on Prognosis and Tumor-Related Inflammation in Renal Clear Cell Carcinoma.Frontiers in genetics · 2021Article
- Tumor progression locus 2 (TPL2) in tumor-promoting Inflammation, Tumorigenesis and Tumor Immunity.Theranostics · 2020Review
- Tpl2 is required for VEGF-A-stimulated signal transduction and endothelial cell function.Biology open · 2019Article
- Tomato lycopene prevention of alcoholic fatty liver disease and hepatocellular carcinoma development.Chronic diseases and translational medicine · 2018Article
- Phytofabrication of Silver nanoparticles: Novel Drug to overcome hepatocellular ailments.Toxicology reports · 2018Article
- miR-589-5p inhibits MAP3K8 and suppresses CD90Journal of experimental & clinical cancer research : CR · 2016Article
- Targeting interleukin-1 receptor-associated kinase 1 for human hepatocellular carcinoma.Journal of experimental & clinical cancer research : CR · 2016Article
- Quercetin sensitizes glioblastoma to t-AUCB by dual inhibition of Hsp27 and COX-2 in vitro and in vivo.Journal of experimental & clinical cancer research : CR · 2016Article
- Deletion of tumor progression locus 2 attenuates alcohol-induced hepatic inflammation.Hepatobiliary surgery and nutrition · 2016Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundTumor progression locus 2 (TPL2), a serine-threonine kinase, functions as a critical regulator of inflammatory pathways and mediates oncogenic events. The potential role of Tpl2 in nonalcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) development remains unknown.
methodsBoth wild-type and Tpl2 knockout male mice were initiated by a hepatic carcinogen (diethylnitrosamine, i.p. with a single dose of 25 mg.kg(-1))at 2 weeks of age, and then were given the high carbohydrate diet feeding to induce hepatic steatosis, inflammation, adenoma and HCC for 24 weeks.
resultsTpl2 knockout mice had significantly lower incidences of liver tumor and developed hepatocellular adenoma only, which is contrast to wild-type mice where they all developed HCC. Tpl2 knockout mice had significantly down-regulated phosphorylation of JNK and ERK, and levels of mRNA expression of pro-inflammatory cytokines (Il-1β, Il-18, Mcp-1 and Nalp3), which correlated with the reduced incidence and number of hepatic inflammatory foci. Furthermore, Tpl2 ablation resulted in decreased hepatic steatosis and expression of de novo lipogenesis related markers (ACC, SCD1, SREBP1C and AKT phosphorylation), as well as reduction of endoplasmic reticulum stress biomarkers PERK and eIF-2a.
conclusionThe study revealed for the first time that Tpl2 plays a significant role in promoting HCC development by its pro-inflammatory effect, which suggested that Tpl2 could be a molecular target for HCC prevention.
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