ArticleJournal of hepatology2018
Shp2 deletion in hepatocytes suppresses hepatocarcinogenesis driven by oncogenic β-Catenin, PIK3CA and MET.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Association between gut microbiota and hepatocellular carcinoma from 2011 to 2022: Bibliometric analysis and global trends.Frontiers in oncology · 2023Pooled it
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Deficiency of PTEN Confers Hypersensitivity to Fatty Acid-Mediated ER Stress in Transformed Hepatocytes.International journal of molecular sciences · 2026Article
- MELGene: knowledge-enhanced multimodel ensemble learning for disease-gene association prediction.Briefings in bioinformatics · 2026Article
- GLP-1RA in JBMMSCs promoted osteogenic differentiation via modulating CREB and BRD4 signaling mediated proliferation and stemness.Scientific reports · 2025Article
- Targeting phase separation: a promising treatment option for hepatocellular carcinoma.Cell communication and signaling : CCS · 2025Review
- Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases.Acta pharmaceutica Sinica. B · 2024Review
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Review
- Targeting Protein Phosphatases for the Treatment of Chronic Liver Disease.Current drug targets · 2024Review
- Hydrodynamic Transfection of Hepatocytes for the Study of Hepatocellular Carcinogenesis.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Liquid-liquid phase separation in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2024Review
- Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors.Frontiers in immunology · 2024Review
- Identification of CD133eLife · 2023Article
- Article
- Curcumin inhibits proliferation of hepatocellular carcinoma cells by blocking PTPN1 and PTPN11 expression.Oncology letters · 2023Article
- Elevated Nuclear PHGDH Synergistically Functions with cMyc to Reshape the Immune Microenvironment of Liver Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- The Immunosuppressive Roles of PD-L1 during Influenza A Virus Infection.International journal of molecular sciences · 2023Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsShp2 is an SH2-tyrosine phosphatase acting downstream of receptor tyrosine kinases (RTKs). Most recent data demonstrated a liver tumor-suppressing role for Shp2, as ablating Shp2 in hepatocytes aggravated hepatocellular carcinoma (HCC) induced by chemical carcinogens or Pten loss. We further investigated the effect of Shp2 deficiency on liver tumorigenesis driven by classical oncoproteins c-Met (receptor for HGF), β-catenin and PIK3CA.
methodsWe performed hydrodynamic tail vein injection of two pairs of plasmids expressing c-Met and ΔN90-β-catenin (MET/CAT), or c-Met and PIK3CA
resultsDespite the induction of oxidative and metabolic stresses, Shp2 deletion in hepatocytes suppressed hepatocarcinogenesis driven by overexpression of oncoproteins MET/CAT or MET/PIK. Shp2 loss inhibited proliferative signaling from c-Met, Wnt/β-catenin, Ras/Erk and PI3K/Akt pathways, but triggered cell senescence following exogenous expression of the oncogenes.
conclusionsShp2, acting downstream of RTKs, is positively required for hepatocyte-intrinsic tumorigenic signaling from these oncoproteins, even if Shp2 deficiency induces a tumor-promoting hepatic microenvironment. These data suggest a new and more effective therapeutic strategy for HCCs driven by oncogenic RTKs and other upstream molecules, by inhibiting Shp2 and also suppressing any tumor-enhancing stromal factors produced because of Shp2 inhibition. LAY SUMMARY: Primary liver cancer is a malignant disease with poor prognosis, largely because there are limited systemic therapies available. We show here that a cytoplasmic tyrosine phosphatase Shp2 is required for liver tumorigenesis. This tumorigenesis is driven by two oncoproteins that are implicated in human liver cancer. This, together with our previous studies, uncovers the complexity of liver tumorigenesis, by elucidating the pro- and anti-tumor effects of Shp2 in mouse models. This data can be used to guide new therapies.
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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 Socratic graph.