ArticleNature communications2015
Inhibition of SHP2-mediated dephosphorylation of Ras suppresses oncogenesis.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 143 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.
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Who cites it
143 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Sphingosine 1-phosphate (S1P) signaling in glioblastoma multiforme-A systematic review.International journal of molecular sciences · 2017Pooled it
- Inhibition of SHP2 enhances the effects of selective receptor tyrosine kinase inhibitors in untreated preclinical models of RET-mutated thyroid cancer.Investigational new drugs · 2026Article
- Precision Targeting ofInternational journal of molecular sciences · 2026Review
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Multiplexed single-cell transcriptomics reveals diverse phenotypic outcomes for pathogenic SHP2 variants.Science advances · 2026Article
- A first-in-human phase 1 study of the SHP2 inhibitor BBP-398 in patients with advanced solid tumors.NPJ precision oncology · 2026Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.EMBO reports · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- A familial modeling framework for advancing precision medicine for children with neuropsychiatric disorders.Developmental medicine and child neurology · 2025Article
- RAS Pathway Inhibitors Combined with Targeted Agents Are Active in Patient-Derived Spheroids with Oncogenic KRAS Variants from Multiple Cancer Types.Cancer research communications · 2025Article
- Proximity-labeling proteomics reveals remodeled interactomes and altered localization of pathogenic SHP2 variants.bioRxiv : the preprint server for biology · 2025Article
- Deep mutational scanning of the multi-domain phosphatase SHP2 reveals mechanisms of regulation and pathogenicity.Nature communications · 2025Article
- RAS Mutations in Advanced Colorectal Cancer: Mechanisms, Clinical Implications, and Novel Therapeutic Approaches.Medicina (Kaunas, Lithuania) · 2025Review
- Targeting SHP2 with Natural Products: Exploring Saponin-Based Allosteric Inhibitors and Their Therapeutic Potential.Current issues in molecular biology · 2025Review
- Integrated multi-omics identify key signalling pathways for notochord lumenogenesis in ascidianOpen biology · 2025Article
- First Results of Migoprotafib, a Potent and Highly Selective Src Homology-2 Domain-Containing Phosphatase 2 Inhibitor in Patients with Advanced Solid Tumors.Molecular cancer therapeutics · 2025Article
- Recent advances in targeted degradation in the RAS pathway.Future medicinal chemistry · 2025Review
- Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.Chemical reviews · 2025Review
- KRAS Mutations in Cancer: Understanding Signaling Pathways to Immune Regulation and the Potential of Immunotherapy.Cancers · 2025Review
83 more citing papers are in PubMed but not listed here.
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 6 institutions in 2 countries.
Funding
Abstract
Ras is phosphorylated on a conserved tyrosine at position 32 within the switch I region via Src kinase. This phosphorylation inhibits the binding of effector Raf while promoting the engagement of GTPase-activating protein (GAP) and GTP hydrolysis. Here we identify SHP2 as the ubiquitously expressed tyrosine phosphatase that preferentially binds to and dephosphorylates Ras to increase its association with Raf and activate downstream proliferative Ras/ERK/MAPK signalling. In comparison to normal astrocytes, SHP2 activity is elevated in astrocytes isolated from glioblastoma multiforme (GBM)-prone H-Ras(12V) knock-in mice as well as in glioma cell lines and patient-derived GBM specimens exhibiting hyperactive Ras. Pharmacologic inhibition of SHP2 activity attenuates cell proliferation, soft-agar colony formation and orthotopic GBM growth in NOD/SCID mice and decelerates the progression of low-grade astrocytoma to GBM in a spontaneous transgenic glioma mouse model. These results identify SHP2 as a direct activator of Ras and a potential therapeutic target for cancers driven by a previously 'undruggable' oncogenic or hyperactive Ras.
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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.