ArticleScientific reports2017
Role of insulin receptor substrates in the progression of hepatocellular carcinoma.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 46 citations in OpenAlex.
- Large-scale, interpretable gene regulatory network inference through biologically informed matrix factorization.bioRxiv : the preprint server for biology · 2026Article
- Differential phosphorylation of PHIP phosphopeptides with implications in insulin signaling.BMC molecular and cell biology · 2026Article
- Dissecting the Phospho-Regulatory Landscape of Protein Kinase N1 (PKN1) and Its Downstream Signaling: Functional Insights into the Activity-Dependent and Disease-Relevant Phosphosites.International journal of molecular sciences · 2026Article
- Identification of novel microRNAs: Biomarkers for pathogenesis of hepatocellular carcinoma in mice model.Biochemistry and biophysics reports · 2025Article
- Worse survival of hepatocellular cancer patients with membranous insulin receptor overexpression.Scientific reports · 2025Article
- Diverting hepatic lipid fluxes with lifestyles revision and pharmacological interventions as a strategy to tackle steatotic liver disease (SLD) and hepatocellular carcinoma (HCC).Nutrition & metabolism · 2024Review
- Article
- PYCR1 promotes liver cancer cell growth and metastasis by regulating IRS1 expression through lactylation modification.Clinical and translational medicine · 2024Article
- Crithmum maritimum Extract Restores Lipid Homeostasis and Metabolic Profile of Liver Cancer Cells to a Normal Phenotype.Plant foods for human nutrition (Dordrecht, Netherlands) · 2024Article
- Weight-centric prevention of cancer.Obesity pillars · 2024Review
- Lifestyle factors, glycemic traits, and lipoprotein traits and risk of liver cancer: a Mendelian randomization analysis.Scientific reports · 2024Article
- Gut insulin action protects from hepatocarcinogenesis in diabetic mice comorbid with nonalcoholic steatohepatitis.Nature communications · 2023Article
- Insulin Receptor Isoforms and Insulin Growth Factor-like Receptors: Implications in Cell Signaling, Carcinogenesis, and Chemoresistance.International journal of molecular sciences · 2023Review
- Clinico-histological and molecular features of hepatocellular carcinoma from nonalcoholic fatty liver disease.Cancer science · 2023Review
- Prognostic role of metformin in diabetes mellitus type 2 patients with hepatocellular carcinoma: A systematic review and meta-analysis.World journal of diabetes · 2023Article
- Review
- B-lymphoid tyrosine kinase-mediated FAM83A phosphorylation elevates pancreatic tumorigenesis through interacting with β-catenin.Signal transduction and targeted therapy · 2023Article
- In Silico Analysis of MicroRNA Expression Data in Liver Cancer.Cancer informatics · 2023Article
- Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.Cancers · 2022Review
- The expression of long non-coding RNA HOTAIR in advanced hepatocellular carcinoma and its prognostic correlation with sunitinib therapy.Archives of medical science : AMS · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several cellular signaling pathways, including insulin/IGF signaling, are known to be activated in hepatocellular carcinoma (HCC). Here, we investigated the roles of insulin receptor substrate (Irs) 1 and Irs2, both of which are the major molecules to be responsible for transducing insulin/IGF signaling in the liver, in the development of HCC by inducing chemical carcinogenesis using diethylnitrosamine (DEN) in mice. The Irs1 mRNA and protein expressions were upregulated in the tumors, along with enhanced insulin signaling. Liver-specific Irs1-knockout (LIrs1KO) mice exhibited suppression of DEN-induced HCC development, accompanied by reduced cancer cell proliferative activity and reduced activation of Akt. Gene expression analyses revealed that the tumors in the DEN-treated LIrs1KO mice showed modest metabolic alterations during hepatocarcinogenesis as well as decreased inflammation and invasion potentials. On the other hand, liver-specific Irs2-knockout (LIrs2KO) mice showed a similar pattern of HCC development to the DEN-treated control wild-type mice. Based on the knowledge that Wnt/β-catenin signaling is activated in HCC, we focused on Wnt/β-catenin signaling and demonstrated that Irs1 expression was induced by Wnt3a stimulation in the primary hepatocytes, associated with insulin-stimulated Akt activation. These data suggest that upregulated Irs1 by Wnt/β-catenin signaling plays a crucial role in the progression of HCC.
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