Mutations leading to constitutive active gp130/JAK1/STAT3 pathway

Cytokine Growth Factor Rev. 2015 Oct;26(5):499-506. doi: 10.1016/j.cytogfr.2015.07.010. Epub 2015 Jul 3.

Abstract

Constitutive activation of STAT (Signal Transducer and Activator of Transcription) transcription factors is a common feature identified in numerous tumors. Inflammatory hepatocellular adenomas (IHCA) are benign liver tumors characterized by an inflammatory phenotype and an overexpression of STAT3 target genes. Recurrent somatic mutations in major actors belonging to the IL6/JAK/STAT3 pathway have been identified in these tumors. (1) 60% of IHCA show IL-6 signal transducer (IL6ST; gp130) mutations; (2) 10% harbor mutations of the Fyn-related kinase FRK; (3) 5% harbor mutations in STAT3; (4) 5% harbor somatic mutations in the GNAS complex locus; and (5) 1% of IHCA harbor mutations in the Janus kinase 1 (JAK1). All these IHCA-associated mutations promote the constitutive activation of STAT3. In this review, we discuss the role of these mutated genes in IHCA and other tumors.

Keywords: FRK; GNAS; Inflammatory hepatocellular adenomas; JAK1; STAT3; gp130.

Publication types

  • Review

MeSH terms

  • Animals
  • Cytokine Receptor gp130* / genetics
  • Cytokine Receptor gp130* / immunology
  • Humans
  • Janus Kinase 1* / genetics
  • Janus Kinase 1* / immunology
  • Mutation*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / immunology
  • Neoplasms* / genetics
  • Neoplasms* / immunology
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / immunology
  • STAT3 Transcription Factor* / genetics
  • STAT3 Transcription Factor* / immunology
  • Signal Transduction* / genetics
  • Signal Transduction* / immunology

Substances

  • IL6ST protein, human
  • Neoplasm Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Cytokine Receptor gp130
  • Protein-Tyrosine Kinases
  • FRK protein, human
  • JAK1 protein, human
  • Janus Kinase 1