ArticleCarcinogenesis2014
SHP2E76K mutant promotes lung tumorigenesis in transgenic mice.
Article in Carcinogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- SHP-2 Expression Is a Positive Prognostic Biomarker in Non-Small-Cell Lung Carcinoma: Association with KRAS Mutation and Prolonged Survival.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- Functional roles of SRC signaling in pancreatic cancer: Recent insights provide novel therapeutic opportunities.Oncogene · 2023Review
- Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Shp2-mediated MAPK pathway regulates ΔNp63 in epithelium to promote corneal innervation and homeostasis.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- SHP2 deficiency promotes Staphylococcus aureus pneumonia following influenza infection.Cell proliferation · 2020Article
- AlloDriver: a method for the identification and analysis of cancer driver targets.Nucleic acids research · 2019Article
- Prevalence and role of HER2 mutations in cancer.Pharmacology & therapeutics · 2019Review
- Gain-Of-Function E76K-Mutant SHP2 Promotes Cell Proliferation, Metastasis, And Tumor Growth In Glioblastoma Through Activation Of The ERK/CREB Pathway.OncoTargets and therapy · 2019Article
- Synthetic lethality of TNK2 inhibition in PTPN11-mutant leukemia.Science signaling · 2018Article
- Shp2 regulates migratory behavior and response to EGFR-TKIs through ERK1/2 pathway activation in non-small cell lung cancer cells.Oncotarget · 2017Article
- SHP2 negatively regulates HLA-ABC and PD-L1 expression via STAT1 phosphorylation in prostate cancer cells.Oncotarget · 2017Article
- Shp2 confers cisplatin resistance in small cell lung cancer via an AKT-mediated increase in CA916798.Oncotarget · 2017Article
- LNDriver: identifying driver genes by integrating mutation and expression data based on gene-gene interaction network.BMC bioinformatics · 2016Article
- Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma.Molecular cancer therapeutics · 2016Article
- Article
- Overexpression of major CDKN3 transcripts is associated with poor survival in lung adenocarcinoma.British journal of cancer · 2015Article
- Expression and clinical significance of tyrosine phosphatase SHP2 in thyroid carcinoma.Oncology letters · 2015Article
- Functions of Shp2 in cancer.Journal of cellular and molecular medicine · 2015Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
Lung cancer is a major disease carrying heterogeneous molecular lesions and many of them remain to be analyzed functionally in vivo. Gain-of-function (GOF) SHP2 (PTPN11) mutations have been found in various types of human cancer, including lung cancer. However, the role of activating SHP2 mutants in lung cancer has not been established. We generated transgenic mice containing a doxycycline (Dox)-inducible activating SHP2 mutant (tetO-SHP2(E76K)) and analyzed the role of SHP2(E76K) in lung tumorigenesis in the Clara cell secretory protein (CCSP)-reverse tetracycline transactivator (rtTA)/tetO-SHP2(E76K) bitransgenic mice. SHP2(E76K) activated Erk1/Erk2 (Erk1/2) and Src, and upregulated c-Myc and Mdm2 in the lungs of bitransgenic mice. Atypical adenomatous hyperplasia and small adenomas were observed in CCSP-rtTA/tetO-SHP2(E76K) bitransgenic mice induced with Dox for 2-6 months and progressed to larger adenoma and adenocarcinoma by 9 months. Dox withdrawal from bitransgenic mice bearing magnetic resonance imaging-detectable lung tumors resulted in tumor regression. These results show that the activating SHP2 mutant promotes lung tumorigenesis and that the SHP2 mutant is required for tumor maintenance in this mouse model of non-small cell lung cancer. SHP2(E76K) was associated with Gab1 in the lung of transgenic mice. Elevated pGab1 was observed in the lung of Dox-induced CCSP-rtTA/tetO-SHP2(E76K) mice and in cell lines expressing SHP2(E76K), indicating that the activating SHP2 mutant autoregulates tyrosine phosphorylation of its own docking protein. Gab1 tyrosine phosphorylation is sensitive to inhibition by the Src inhibitor dasatinib in GOF SHP2-mutant-expressing cells, suggesting that Src family kinases are involved in SHP2 mutant-induced Gab1 tyrosine phosphorylation.
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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.