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Cited by 332Protein Tyrosine PhosphatasesCytokine Signaling Pathways and InteractionsLiver physiology and pathology

Ptpn11/Shp2 Acts as a Tumor Suppressor in Hepatocellular Carcinogenesis

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Bard-Chapeau, Emilie A., Li, Shuangwei, Ding, Jin, Zhang, Sharon S., Zhu, Helen H., Princen, Frederic, Fang, Diane D., Han, Tao +5 more·2011·Cancer Cell
DOI 10.1016/j.ccr.2011.03.023PMC PMC3098128
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Abstract

The human gene Ptpn11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia. Herein we report a tumor-suppressor function of Shp2. Hepatocyte-specific deletion of Shp2 promotes inflammatory signaling through the Stat3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and development of tumors in aged mice. Furthermore, Shp2 ablation dramatically enhanced diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) development, which was abolished by concurrent deletion of Shp2 and Stat3 in hepatocytes. Decreased Shp2 expression was detected in a subfraction of human HCC specimens. Thus, in contrast to the leukemogenic effect of dominant-active mutants, Ptpn11/Shp2 has a tumor-suppressor function in liver.

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  • STAT3 may serve as a common signalling node in development of HCC associated with diverse etiologies, including viral infection, and metabolic and hormonal dysregulation.

    “In defining a central role for STAT3 in FGF19-driven hepatocarcinogenesis, the data presented in this report extend previous findings on the causal role played by STAT3 in hepatocellular tumorigenesis4445, and suggest that STAT3 may serve as a common signalling node in the development of HCC associated with diverse etiologies, including viral infection, and metabolic and hormonal dysregulation.”

    From Non-cell-autonomous activation of IL-6/STAT3 signaling mediates FGF19-driven hepatocarcinogenesis (2017) · cites this paper as [45]

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Authors
Bard-Chapeau, E. A., Li, S., Ding, J., Zhang, S. S., Zhu, H. H., Princen, F., Fang, D. D., Han, T., Bailly-Maitre, B., Poli, V., Varki, N. M., Wang, H., & Feng, G.-S.
Affiliations
  • Sanford Burnham Prebys Medical Discovery Institute (US)
  • University of California San Diego (US)
  • Second Military Medical University (CN)
  • University of Turin (IT)
Corresponding author
Feng, Gen-Sheng
ORCID
Venue
Cancer Cell
Publisher
Elsevier BV
Published
2011-05
Volume
19
Issue
5
Pages
629-639
ISSN
1535-6108 (ISSN-L)
DOI
10.1016/j.ccr.2011.03.023
PMC
PMC3098128
OpenAlex
W2137135537
Cited by
332
References
3
Citations by year
2026: 4 · 2025: 15 · 2024: 17 · 2023: 25 · 2022: 21 · 2021: 26 · 2020: 17 · 2019: 17 · 2018: 25 · 2017: 27 · 2016: 23 · 2015: 27 · 2014: 29 · 2013: 30 · 2012: 23
FWCI
11.44
Type
journal article
Language
en
Open access
Licence
Locations
  • Cancer Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Funders
  • National Natural Science Foundation of China (30921006)
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK75916, R01DK73945, R01DK075916, R01DK073945)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
PTPN11, SHP2, tumor suppressor, hepatocellular carcinoma, hepatocarcinogenesis, STAT3 signaling, liver inflammation, hepatocyte-specific gene deletion, diethylnitrosamine, regenerative hyperplasia, liver necrosis, protein tyrosine phosphatase
MeSH terms
Proto-Oncogene Mas, Animals, Diethylnitrosamine, Gene Expression Regulation, Hepatitis, Carcinoma, Hepatocellular, Humans, Hyperplasia, Lipopolysaccharides, Liver, Liver Neoplasms, Liver Regeneration, Male, Mice, Inbred C57BL, Necrosis, Time Factors, Signal Transduction, Interleukin-6, Cytokines, Adenoma, Liver Cell, Mice, Knockout, Inflammation Mediators, Tumor Suppressor Proteins, STAT3 Transcription Factor, Mice, Protein Tyrosine Phosphatase, Non-Receptor Type 11

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