ArticleNeuro-oncology2020
ΔNp73/ETS2 complex drives glioblastoma pathogenesis- targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma.
Article in Neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 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.
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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
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Glioblastoma research on zebrafish xenograft models: a systematic review.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Pooled it
- S100A9 enhances tumor immune suppression and cancer cell survival in small cell lung cancer.Cell death & disease · 2025Article
- Targeting racial disparities in breast cancer: mechanistic insights and therapeutic potential of African medicinal plants.Medical oncology (Northwood, London, England) · 2025Review
- The Tie2 antagonist rebastinib reduces ovarian cancer growth in a syngeneic murine model.BMC cancer · 2025Article
- Enhancing immunotherapy efficacy in colorectal cancer: targeting the FGR-AKT-SP1-DKK1 axis with DCC-2036 (Rebastinib).Cell death & disease · 2025Article
- DNp73 enhances tumor progression and immune evasion in multiple myeloma by targeting the MYC and MYCN pathways.Frontiers in immunology · 2024Article
- MicroRNA and mRNA Expression Changes in Glioblastoma Cells Cultivated under Conditions of Neurosphere Formation.Current issues in molecular biology · 2022Article
- Different Approaches for the Profiling of Cancer Pathway-Related Genes in Glioblastoma Cells.International journal of molecular sciences · 2022Article
- Zebrafish Models of Paediatric Brain Tumours.International journal of molecular sciences · 2022Review
- cPLA2 blockade attenuates S100A7-mediated breast tumorigenicity by inhibiting the immunosuppressive tumor microenvironment.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- The p53 family member p73 in the regulation of cell stress response.Biology direct · 2021Review
- Integrative analysis of TP73 profile prognostic significance in WHO grade II/III glioma.Cancer medicine · 2021Article
- Gene Regulatory Network of ETS Domain Transcription Factors in Different Stages of Glioma.Journal of personalized medicine · 2021Article
- Receptor Tyrosine Kinase Signaling and Targeting in Glioblastoma Multiforme.International journal of molecular sciences · 2021Review
- Mechanisms of Functional Pleiotropy of p73 in Cancer and Beyond.Frontiers in cell and developmental biology · 2021Review
- Racially Disparate Expression of mTOR/ERK-1/2 Allied Proteins in Cancer.Frontiers in cell and developmental biology · 2021Review
- Review
- Macrophage migration inhibitory factor inhibition as a novel therapeutic approach against triple-negative breast cancer.Cell death & disease · 2020Article
- Modeling Cancer Using Zebrafish Xenografts: Drawbacks for Mimicking the Human Microenvironment.Cells · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma (GBM) remains one of the least successfully treated cancers. It is essential to understand the basic biology of this lethal disease and investigate novel pharmacological targets to treat GBM. The aims of this study were to determine the biological consequences of elevated expression of ΔNp73, an N-terminal truncated isoform of TP73, and to evaluate targeting of its downstream mediators, the angiopoietin 1 (ANGPT1)/tunica interna endothelial cell kinase 2 (Tie2) axis, by using a highly potent, orally available small-molecule inhibitor (rebastinib) in GBM.
methodsΔNp73 expression was assessed in glioma sphere cultures, xenograft glioblastoma tumors, and glioblastoma patients by western blot, quantitative reverse transcription PCR, and immunohistochemistry. Immunoprecipitation, chromatin immunoprecipitation (ChiP) and sequential ChIP were performed to determine the interaction between ΔNp73 and E26 transformation-specific (ETS) proto-oncogene 2 (ETS2) proteins. The oncogenic consequences of ΔNp73 expression in glioblastomas were examined by in vitro and in vivo experiments, including orthotopic zebrafish and mouse intracranial-injection models. Effects of rebastinib on growth of established tumors and survival were examined in an intracranial-injection mouse model.
resultsΔNp73 upregulates both ANGPT1 and Tie2 transcriptionally through ETS conserved binding sites on the promoters by interacting with ETS2. Elevated expression of ΔNp73 promotes tumor progression by mediating angiogenesis and survival. Therapeutic targeting of downstream ΔNp73 signaling pathways by rebastinib inhibits growth of established tumors and extends survival in preclinical models of glioblastoma.
conclusionAberrant expression of ΔNp73 in GBM promotes tumor progression through autocrine and paracrine signaling dependent on Tie2 activation by ANGPT1. Disruption of this signaling by rebastinib improves tumor response to treatment in glioblastoma.
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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.