ArticleScientific reports2016
Wip1 inhibitor GSK2830371 inhibits neuroblastoma growth by inducing Chk2/p53-mediated apoptosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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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
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
- PPM1D mutations are oncogenic drivers of de novo diffuse midline glioma formation.Nature communications · 2022Article
- Article
- Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies.Cancers · 2021Review
- MiR-145-5p Inhibits the Invasion of Prostate Cancer and Induces Apoptosis by Inhibiting WIP1.Journal of oncology · 2021Article
- Her2 promotes early dissemination of breast cancer by suppressing the p38-MK2-Hsp27 pathway that is targetable by Wip1 inhibition.Oncogene · 2020Article
- Wild-type p53-induced phosphatase 1 promotes vascular smooth muscle cell proliferation and neointima hyperplasia after vascular injury via p-adenosine 5'-monophosphate-activated protein kinase/mammalian target of rapamycin complex 1 pathway.Journal of hypertension · 2019Article
- Article
- Small molecule activators of the p53 response.Journal of molecular cell biology · 2019Review
- Dodging the bullet: therapeutic resistance mechanisms in pediatric cancers.Cancer drug resistance (Alhambra, Calif.) · 2019Review
- P53/PUMA are potential targets that mediate the protection of brain-derived neurotrophic factor (BDNF)/TrkB from etoposide-induced cell death in neuroblastoma (NB).Apoptosis : an international journal on programmed cell death · 2018Article
- An evaluationOncotarget · 2018Article
- ATR kinase regulates its attenuation via PPM1D phosphatase recruitment to chromatin during recovery from DNA replication stress signalling.Journal of biosciences · 2018Article
- Small molecule inhibitor regorafenib inhibits RET signaling in neuroblastoma cells and effectively suppresses tumor growthOncotarget · 2017Article
- WIP1 phosphatase as pharmacological target in cancer therapy.Journal of molecular medicine (Berlin, Germany) · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 7 institutions in 2 countries.
Funding
Abstract
Neuroblastoma (NB) is the most common extracranial tumor in children. Unlike in most adult tumors, tumor suppressor protein 53 (p53) mutations occur with a relatively low frequency in NB and the downstream function of p53 is intact in NB cell lines. Wip1 is a negative regulator of p53 and hindrance of Wip1 activity by novel inhibitor GSK2830371 is a potential strategy to activate p53's tumor suppressing function in NB. Yet, the in vivo efficacy and the possible mechanisms of GSK2830371 in NB have not yet been elucidated. Here we report that novel Wip1 inhibitor GSK2830371 induced Chk2/p53-mediated apoptosis in NB cells in a p53-dependent manner. In addition, GSK2830371 suppressed the colony-formation potential of p53 wild-type NB cell lines. Furthermore, GSK2830371 enhanced doxorubicin- (Dox) and etoposide- (VP-16) induced cytotoxicity in a subset of NB cell lines, including the chemoresistant LA-N-6 cell line. More importantly, GSK2830371 significantly inhibited tumor growth in an orthotopic xenograft NB mouse model by inducing Chk2/p53-mediated apoptosis in vivo. Taken together, this study suggests that GSK2830371 induces Chk2/p53-mediated apoptosis both in vitro and in vivo in a p53 dependent manner.
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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.