Role of insulin receptor substrates in the progression of hepatocellular carcinoma View Full Text


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Article Info

DATE

2017-07-14

AUTHORS

Yoshitaka Sakurai, Naoto Kubota, Iseki Takamoto, Atsushi Obata, Masahiko Iwamoto, Takanori Hayashi, Masakazu Aihara, Tetsuya Kubota, Hiroshi Nishihara, Takashi Kadowaki

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. More... »

PAGES

5387

References to SciGraph publications

  • 2013-07-09. Insulin enhances metabolic capacities of cancer cells by dual regulation of glycolytic enzyme pyruvate kinase M2 in MOLECULAR CANCER
  • 1999-11. Immunocytochemical investigation of catalase and peroxisomal lipid β-oxidation enzymes in human hepatocellular tumors and liver cirrhosis in VIRCHOWS ARCHIV
  • 2010-07-19. The role of signaling pathways in the development and treatment of hepatocellular carcinoma in ONCOGENE
  • 2012-11-20. Combined targeting of AKT and mTOR synergistically inhibits proliferation of hepatocellular carcinoma cells in MOLECULAR CANCER
  • 2011-09-07. Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in hepatic glucose metabolism in DIABETOLOGIA
  • 2016-10-06. Differential hepatic distribution of insulin receptor substrates causes selective insulin resistance in diabetes and obesity in NATURE COMMUNICATIONS
  • 2010-10-19. Growth hormone, the insulin-like growth factor axis, insulin and cancer risk in NATURE REVIEWS ENDOCRINOLOGY
  • 2015-08-13. TRB3 links insulin/IGF to tumour promotion by interacting with p62 and impeding autophagic/proteasomal degradations in NATURE COMMUNICATIONS
  • 2006-02-01. Critical nodes in signalling pathways: insights into insulin action in NATURE REVIEWS MOLECULAR CELL BIOLOGY
  • 2013-12-08. TCF7L2 in mouse pancreatic beta cells plays a crucial role in glucose homeostasis by regulating beta cell mass in DIABETOLOGIA
  • 2004-11-21. Application of comparative functional genomics to identify best-fit mouse models to study human cancer in NATURE GENETICS
  • 2001-12. Insulin signalling and the regulation of glucose and lipid metabolism in NATURE
  • 2012-09-07. Protection from non-alcoholic steatohepatitis and liver tumourigenesis in high fat-fed insulin receptor substrate-1-knockout mice despite insulin resistance in DIABETOLOGIA
  • 2004-08. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms in NATURE REVIEWS CANCER
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    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-017-03299-3

    DOI

    http://dx.doi.org/10.1038/s41598-017-03299-3

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1090627087

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28710407


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