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Cited by 477Cytokine Signaling Pathways and InteractionsLiver physiology and pathologyHepatocellular Carcinoma Treatment and Prognosis

Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours

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Rebouissou, Sandra, Amessou, Mohamed, Couchy, Gabrielle, Poussin, Karine, Imbeaud, Sandrine, Pilati, Camilla, Izard, Tina, Balabaud, Charles +2 more·2009·Nature
DOI 10.1038/nature07475PMC PMC2695248
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Abstract

Inflammatory hepatocellular adenomas are benign liver tumours defined by the presence of inflammatory infiltrates and by the increased expression of inflammatory proteins in tumour hepatocytes. Here we show a marked activation of the interleukin (IL)-6 signalling pathway in this tumour type; sequencing candidate genes pinpointed this response to somatic gain-of-function mutations in the IL6ST gene, which encodes the signalling co-receptor gp130. Indeed, 60% of inflammatory hepatocellular adenomas harbour small in-frame deletions that target the binding site of gp130 for IL-6, and expression of four different gp130 mutants in hepatocellular cells activates signal transducer and activator of transcription 3 (STAT3) in the absence of ligand. Furthermore, analysis of hepatocellular carcinomas revealed that rare gp130 alterations are always accompanied by beta-catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant conversion of hepatocytes. The recurrent gain-of-function gp130 mutations in these human hepatocellular adenomas fully explains activation of the acute inflammatory phase observed in tumourous hepatocytes, and suggests that similar alterations may occur in other inflammatory epithelial tumours with STAT3 activation.

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  • Somatic gain-of-function mutations in gp130 that activate gp130-STAT3 signaling lead to inflammatory hepatocellular tumors.

    “Somatic GOF mutations in gp130 that activate gp130–STAT3 signaling lead to inflammatory hepatocellular tumors (272).”

    From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [272]

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Research works printed but not linked: 32

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Authors
Rebouissou, S., Amessou, M., Couchy, G., Poussin, K., Imbeaud, S., Pilati, C., Izard, T., Balabaud, C., Bioulac-Sage, P., & Zucman-Rossi, J.
Affiliations
  • Inserm (FR)
  • Université Paris-Sud (FR)
  • Scripps Research Institute (US)
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2008-11-19
Volume
457
Issue
7226
Pages
200-204
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature07475
PMC
PMC2695248
OpenAlex
W2007268662
Cited by
477
References
2
Citations by year
2026: 7 · 2025: 8 · 2024: 12 · 2023: 16 · 2022: 10 · 2021: 22 · 2020: 23 · 2019: 15 · 2018: 26 · 2017: 36 · 2016: 28 · 2015: 34 · 2014: 32 · 2013: 36 · 2012: 48
FWCI
21.86
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institute of General Medical Sciences (R01GM071596, GM 071596)
  • National Institute of Allergy and Infectious Diseases (AI067949, AI055894, R01AI067949, R01AI055894)
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
  • Health Sciences › Medicine › Hepatology › Hepatocellular Carcinoma Treatment and Prognosis
Keywords
gp130, inflammatory hepatocellular adenoma, hepatocellular carcinoma, somatic deletions, gain-of-function mutations, STAT3 activation, CTNNB1 mutation, chronic inflammation and cancer, carcinogenesis
MeSH terms
Humans, Inflammation, Interferons, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, Sequence Deletion, Adenoma, Liver Cell, Gene Expression Profiling, Cell Line, Tumor, STAT3 Transcription Factor, Cytokine Receptor gp130

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