ArticleThe Journal of experimental medicine2011
Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas.
Article in The Journal of experimental medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
120 citing papers in PubMed, 234 citations in OpenAlex.
- IL-12p40 drives oral squamous cell carcinoma progression via MMPs and IL-12Rβ1/STAT3 signaling.Cancer cell international · 2026Article
- Cancer-Associated STAT3 Mutations Maintain ES Cell Self-Renewal Through Phosphorylation-Independent Mechanisms.Genes to cells : devoted to molecular & cellular mechanisms · 2026Article
- Breaking the bonds: targeting protein dimerization for prostate cancer therapy.Endocrinology · 2026Review
- Driver mutation impact in Chinese hepatocellular carcinoma.PloS one · 2026Article
- Molecular Insights into the Diagnosis of Anaplastic Large Cell Lymphoma: Beyond Morphology and Immunophenotype.International journal of molecular sciences · 2025Review
- Phase I Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3, in Patients with Advanced Solid Tumors.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Advances of signal transducer and activator of transcription 3 inhibitors in acute myeloid leukemia (Review).Oncology letters · 2025Review
- Functional validation of a novel STAT3 'variant of unknown significance' identifies a new case of STAT3 GOF syndrome and reveals broad immune cell defects.Clinical and experimental immunology · 2025Article
- Functional screening of somatic mutant events in extranodal natural killer/T-cell lymphoma with adrenal involvement.Frontiers in immunology · 2025Article
- Mechanisms and therapeutic prospect of the JAK-STAT signaling pathway in liver cancer.Molecular and cellular biochemistry · 2025Review
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Study of sex-biased differences in genomic profiles in East Asian hepatocellular carcinoma.Discover oncology · 2024Article
- Article
- Genetics of liver disease in adults.Hepatology communications · 2024Review
- Direct and biologically significant interactions of human herpesvirus 8 interferon regulatory factor 1 with STAT3 and Janus kinase TYK2.PLoS pathogens · 2023Article
- Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications.International journal of molecular sciences · 2023Review
- The ups and downs of STAT3 function: too much, too little and human immune dysregulation.Clinical and experimental immunology · 2023Review
- Crosstalk of Inflammatory Cytokines within the Breast Tumor Microenvironment.International journal of molecular sciences · 2023Review
- Benign liver tumours: understanding molecular physiology to adapt clinical management.Nature reviews. Gastroenterology & hepatology · 2022Review
- Histone H1.2 promotes hepatocarcinogenesis by regulating signal transducer and activator of transcription 3 signaling.Cancer science · 2022Article
60 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Inflammatory hepatocellular adenomas (IHCAs) are benign liver tumors. 60% of these tumors have IL-6 signal transducer (IL6ST; gp130) mutations that activate interleukin 6 (IL-6) signaling. Here, we report that 12% of IHCA subsets lacking IL6ST mutations harbor somatic signal transducer and activator of transcription 3 (STAT3) mutations (6/49). Most of these mutations are amino acid substitutions in the SH2 domain that directs STAT3 dimerization. In contrast to wild-type STAT3, IHCA STAT3 mutants constitutively activated the IL-6 signaling pathway independent of ligand in hepatocellular cells. Indeed, the IHCA STAT3 Y640 mutant homodimerized independent of IL-6 and was hypersensitive to IL-6 stimulation. This was associated with phosphorylation of tyrosine 705, a residue required for IL-6-induced STAT3 activation. Silencing or inhibiting the tyrosine kinases JAK1 or Src, which phosphorylate STAT3, impaired constitutive activity of IHCA STAT3 mutants in hepatocellular cells. Thus, we identified for the first time somatic STAT3 mutations in human tumors, revealing a new mechanism of recurrent STAT3 activation and underscoring the role of the IL-6-STAT3 pathway in benign hepatocellular tumorigenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.