ArticleThe Journal of clinical investigation2011
SHP-2/PTPN11 mediates gliomagenesis driven by PDGFRA and INK4A/ARF aberrations in mice and humans.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- Targeting PDGFRA-SHP2 signaling enhances radiotherapy in IDH1-mutant glioma.Neuro-oncology · 2025Article
- Multi-scale signaling and tumor evolution in high-grade gliomas.Cancer cell · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Targeting TRIM24 promotes neuroblastoma differentiation and decreases tumorigenicity via LSD1/CoREST complex.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Tumor radiogenomics in gliomas with Bayesian layered variable selection.Medical image analysis · 2023Article
- PD-1 receptor outside the main paradigm: tumour-intrinsic role and clinical implications for checkpoint blockade.British journal of cancer · 2023Review
- Oncogenic long noncoding RNA LINC02283 enhances PDGF receptor A-mediated signaling and drives glioblastoma tumorigenesis.Neuro-oncology · 2023Article
- Long-term environmental metal exposure is associated with hypomethylation of CpG sites in NFKB1 and other genes related to oncogenesis.Clinical epigenetics · 2023Article
- Identification of novel proteins for lacunar stroke by integrating genome-wide association data and human brain proteomes.BMC medicine · 2022Article
- Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy.Frontiers in oncology · 2022Review
- Current understanding of gliomagenesis: from model to mechanism.International journal of medical sciences · 2022Review
- Probabilistic edge inference of gene networks with markov random field-based bayesian learning.Frontiers in genetics · 2022Article
- Rates and Patterns of Clonal Oncogenic Mutations in the Normal Human Brain.Cancer discovery · 2022Article
- Prenatal overexpression of platelet-derived growth factor receptor A results in central nervous system hypomyelination.Brain and behavior · 2021Article
- The HIF1α-PDGFD-PDGFRα axis controls glioblastoma growth at normoxia/mild-hypoxia and confers sensitivity to targeted therapy by echinomycin.Journal of experimental & clinical cancer research : CR · 2021Article
- Non-canonical PD-1 signaling in cancer and its potential implications in clinic.Journal for immunotherapy of cancer · 2021Review
- Genetic characterization of an aggressive optic nerve pilocytic glioma.Brain tumor pathology · 2021Article
- PD-L1 promotes tumor growth and progression by activating WIP and β-catenin signaling pathways and predicts poor prognosis in lung cancer.Cell death & disease · 2020Article
- Pediatric low-grade glioma in the era of molecular diagnostics.Acta neuropathologica communications · 2020Review
- SHP-2-Mediated Upregulation of ZEB1 Is Important for PDGF-B-Induced Cell Proliferation and Metastatic Phenotype in Triple Negative Breast Cancer.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 3 countries.
Funding
Abstract
Recent collaborative efforts have subclassified malignant glioblastomas into 4 clinical relevant subtypes based on their signature genetic lesions. Platelet-derived growth factor receptor α (PDGFRA) overexpression is concomitant with a loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) locus (encoding P16INK4A and P14ARF) in a large number of tumors within one subtype of glioblastomas. Here we report that activation of PDGFRα conferred tumorigenicity to Ink4a/Arf-deficient mouse astrocytes and human glioma cells in the brain. Restoration of p16INK4a but not p19ARF suppressed PDGFRα-promoted glioma formation. Mechanistically, abrogation of signaling modules in PDGFRα that lost capacity to bind to SHP-2 or PI3K significantly diminished PDGFRα-promoted tumorigenesis. Furthermore, inhibition of SHP-2 by shRNAs or pharmacological inhibitors disrupted the interaction of PI3K with PDGFRα, suppressed downstream AKT/mTOR activation, and impaired tumorigenesis of Ink4a/Arf-null cells, whereas expression of an activated PI3K mutant rescued the effect of SHP-2 inhibition on tumorigenicity. PDGFRα and PDGF-A are coexpressed in clinical glioblastoma specimens, and such co-expression is linked with activation of SHP-2/AKT/mTOR signaling. Together, our data suggest that in glioblastomas with Ink4a/Arf deficiency, overexpressed PDGFRα promotes tumorigenesis through the PI3K/AKT/mTOR-mediated pathway regulated by SHP-2 activity. These findings functionally validate the genomic analysis of glioblastomas and identify SHP-2 as a potential target for treatment of glioblastomas.
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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.