The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas
Open accessAbstract
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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Cites
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Frequent in-frame somatic deletions activate gp130 in inflammatory hepatocellular tumours
Rebouissou, S., Amessou, M., Couchy, G., Poussin, K., Imbeaud, S., Pilati, C., Izard, T., Balabaud, C., Bioulac-Sage, P., & Zucman-Rossi, J. (2009) · Nature · doi:10.1038/nature07475 · Cited by 477
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Cited by
Imai, M., Watanabe, T., Hatta, M., Das, S. C., Ozawa, M., Shinya, K., Zhong, G., Hanson, A., Katsura, H., Watanabe, S., et al. (2012) · Nature · doi:10.1038/nature10831 · Cited by 1,523
Mechanisms and consequences of Jak–STAT signaling in the immune system
Villarino, A. V., Kanno, Y., & O'Shea, J. J. (2017) · Nature Immunology · doi:10.1038/ni.3691 · Cited by 1,221
IL-6 pathway in the liver: From physiopathology to therapy
Schmidt-Arras, D., & Rose-John, S. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2016.02.004 · Cited by 881
Nault, J. C., Mallet, M., Pilati, C., Calderaro, J., Bioulac-Sage, P., Laurent, C., Laurent, A., Cherqui, D., Balabaud, C., & Zucman-Rossi, J. (2013) · Nature Communications · doi:10.1038/ncomms3218 · Cited by 695
Self-citationThe two faces of IL-6 in the tumor microenvironment
Fisher, D. T., Appenheimer, M. M., & Evans, S. S. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.01.008 · Cited by 693
Metadata
- Authors
- Pilati, C., Amessou, M., Bihl, M. P., Balabaud, C., Van Nhieu, J. T., Paradis, V., Nault, J. C., Izard, T., Bioulac-Sage, P., Couchy, G., Poussin, K., & Zucman-Rossi, J.
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2011-06-20
- Volume
- 208
- Issue
- 7
- Pages
- 1359-1366
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- OpenAlex
- W2128387672
- Cited by
- 242
- References
- 7
- FWCI
- 12.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pilati, C., Amessou, M., Bihl, M. P., Balabaud, C., Van Nhieu, J. T., Paradis, V., Nault, J. C., Izard, T., Bioulac-Sage, P., Couchy, G., Poussin, K., & Zucman-Rossi, J. (2011). Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. Journal of Experimental Medicine. https://doi.org/10.1084/jem.20110283
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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