ArticleOncogene2016
SHP-2-upregulated ZEB1 is important for PDGFRα-driven glioma epithelial-mesenchymal transition and invasion in mice and humans.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 91 citations in OpenAlex.
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- Valtrate, an iridoid compound in Valeriana, elicits anti-glioblastoma activity through inhibition of the PDGFRA/MEK/ERK signaling pathway.Journal of translational medicine · 2023Article
- Regulation of temozolomide resistance via lncRNAs: Clinical and biological properties of lncRNAs in gliomas (Review).International journal of oncology · 2022Review
- MYCN protein stability is a better prognostic indicator in neuroblastoma.BMC pediatrics · 2022Article
- Platelets involved tumor cell EMT during circulation: communications and interventions.Cell communication and signaling : CCS · 2022Review
- Tumor Microenvironment in Glioma Invasion.Brain sciences · 2022Review
- Gliosarcoma vs. glioblastoma: a retrospective case series using molecular profiling.BMC neurology · 2021Article
- Novel insights into the interaction between long non-coding RNAs and microRNAs in glioma.Molecular and cellular biochemistry · 2021Review
- Crosstalk between 17β-Estradiol and TGF-β Signaling Modulates Glioblastoma Progression.Brain sciences · 2021Article
- Targeting of glioma stem-like cells with a parthenolide derivative ACT001 through inhibition of AEBP1/PI3K/AKT signaling.Theranostics · 2021Article
- Identification of low-dose radiation-induced exosomal circ-METRN and miR-4709-3p/GRB14/PDGFRα pathway as a key regulatory mechanism in Glioblastoma progression and radioresistance: Functional validation and clinical theranostic significance.International journal of biological sciences · 2021Article
- Article
- Curse of the devil: molecular insights into the emergence of transmissible cancers in the Tasmanian devil (Sarcophilus harrisii).Cellular and molecular life sciences : CMLS · 2020Review
- SHP-2-Induced Activation of c-Myc Is Involved in PDGF-B-Regulated Cell Proliferation and Angiogenesis in RMECs.Frontiers in physiology · 2020Article
- Review
- TGF-β-activated lncRNA LINC00115 is a critical regulator of glioma stem-like cell tumorigenicity.EMBO reports · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Gliomas are highly malignant brain tumors that are highly invasive and resistant to conventional therapy. Receptor tyrosine kinases (RTKs) such as PDGFRα (platelet-derived growth factor receptor-α), which show frequent aberrant activation in gliomas, are associated with a process of epithelial-mesenchymal transition (EMT), a cellular alteration that confers a more invasive and drug-resistant phenotype. Although this phenomenon is well documented in human cancers, the processes by which RTKs including PDGFRα mediate EMT are largely unknown. Here, we report that SHP-2 (encoded by PTPN11) upregulates an EMT inducer, ZEB1, to mediate PDGFRα-driven glioma EMT, invasion and growth in glioma cell lines and patient-derived glioma stem cells (GSCs) using cell culture and orthotopic xenograft models. ZEB1 and activated PDGFRα were coexpressed in invasive regions of mouse glioma xenografts and clinical glioma specimens. Glioma patients with high levels of both phospho-PDGFRα (p-PDGFRα) and ZEB1 had significantly shorter overall survival compared with those with low expression of p-PDGFRα and ZEB1. Knockdown of ZEB1 inhibited PDGFA/PDGFRα-stimulated glioma EMT, tumor growth and invasion in glioma cell lines and patient-derived GSCs. PDGFRα mutant deficient of SHP2 binding (PDGFRα-F720) or phosphoinositide 3-kinase (PI3K) binding (PDGFRα-F731/42), knockdown of SHP2 or treatments of pharmacological inhibitor for PDGFRα-signaling effectors attenuated PDGFA/PDGFRα-stimulated ZEB1 expression, cell migration and GSC proliferation. Importantly, SHP-2 acts together with PI3K/AKT to regulate a ZEB1-miR-200 feedback loop in PDGFRα-driven gliomas. Taken together, our findings uncover a new pathway in which ZEB1 functions as a key regulator for PDGFRα-driven glioma EMT, invasiveness and growth, suggesting that ZEB1 is a promising therapeutic target for treating gliomas with high PDGFRα activation.
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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.