ArticleOncotarget2015
Inhibition of Shp2 suppresses mutant EGFR-induced lung tumors in transgenic mouse model of lung adenocarcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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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
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Prognostic significance of SHP2 (PTPN11) expression in solid tumors: A meta-analysis.PloS one · 2022Pooled it
- SHP2 promotes osteosarcoma via regulating STAT3/TET3/HOXB2 signaling.Scientific reports · 2026Article
- Identification of alkynyl nicotinamide HSN748 as a RET solvent-front mutant inhibitor with intracranial efficacy.RSC medicinal chemistry · 2025Article
- Setting sail: Maneuvering SHP2 activity and its effects in cancer.Advances in cancer research · 2023Review
- Therapeutic efficacy of the novel SHP2 degrader SHP2-D26, alone or in combination, against lung cancer is associated with modulation of p70S6K/S6, Bim and Mcl-1.Cancer gene therapy · 2022Article
- A comprehensive review of SHP2 and its role in cancer.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- A highly multiplexed quantitative phosphosite assay for biology and preclinical studies.Molecular systems biology · 2021Article
- A structural perspective on targeting the RTK/Ras/MAP kinase pathway in cancer.Protein science : a publication of the Protein Society · 2021Review
- Role of the Tyrosine Phosphatase SHP-2 in Mediating Adrenomedullin Proangiogenic Activity in Solid Tumors.Frontiers in oncology · 2021Article
- Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma.Cell · 2020Article
- Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types.Investigational new drugs · 2019Article
- Article
- Synergistic effects of SHP2 and PI3K pathway inhibitors in GAB2-overexpressing ovarian cancer.American journal of cancer research · 2019Article
- The prognostic significance of SHP2 and its binding protein Hook1 in non-small cell lung cancer.OncoTargets and therapy · 2019Article
- Mutant KRAS-driven cancers depend on PTPN11/SHP2 phosphatase.Nature medicine · 2018Article
- Selective inhibition of leukemia-associated SHP2Leukemia · 2018Article
- Article
- Understanding and Resetting Radiation Sensitivity in Rectal Cancer.Annals of surgery · 2017Article
- Genetic defects of the IRF1-mediated major histocompatibility complex class I antigen presentation pathway occur prevalently in theOncotarget · 2017Article
- Shp2 Plays a Critical Role in IL-6-Induced EMT in Breast Cancer Cells.International journal of molecular sciences · 2017Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Epidermal growth factor receptor (EGFR) mutants drive lung tumorigenesis and are targeted for therapy. However, resistance to EGFR inhibitors has been observed, in which the mutant EGFR remains active. Thus, it is important to uncover mediators of EGFR mutant-driven lung tumors to develop new treatment strategies. The protein tyrosine phosphatase (PTP) Shp2 mediates EGF signaling. Nevertheless, it is unclear if Shp2 is activated by oncogenic EGFR mutants in lung carcinoma or if inhibiting the Shp2 PTP activity can suppress EGFR mutant-induced lung adenocarcinoma. Here, we generated transgenic mice containing a doxycycline (Dox)-inducible PTP-defective Shp2 mutant (tetO-Shp2CSDA). Using the rat Clara cell secretory protein (CCSP)-rtTA-directed transgene expression in the type II lung pneumocytes of transgenic mice, we found that the Gab1-Shp2 pathway was activated by EGFRL858R in the lungs of transgenic mice. Consistently, the Gab1-Shp2 pathway was activated in human lung adenocarcinoma cells containing mutant EGFR. Importantly, Shp2CSDA inhibited EGFRL858R-induced lung adenocarcinoma in transgenic animals. Analysis of lung tissues showed that Shp2CSDA suppressed Gab1 tyrosine phosphorylation and Gab1-Shp2 association, suggesting that Shp2 modulates a positive feedback loop to regulate its own activity. These results show that inhibition of the Shp2 PTP activity impairs mutant EGFR signaling and suppresses EGFRL858R-driven lung adenocarcinoma.
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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.