ArticleOncogene2016
WIP1 modulates responsiveness to Sonic Hedgehog signaling in neuronal precursor cells and medulloblastoma.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Cancer Stem Cell Regulation as a Target of Therapeutic Intervention: Insights into Breast, Cervical and Lung Cancer.Cell biochemistry and biophysics · 2025Review
- Circular extrachromosomal DNA promotes tumor heterogeneity in high-risk medulloblastoma.Nature genetics · 2023Article
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- PPM1D in Solid and Hematologic Malignancies: Friend and Foe?Molecular cancer research : MCR · 2022Article
- Medulloblastoma and the DNA Damage Response.Frontiers in oncology · 2022Review
- Article
- High Expression ofCancers · 2021Article
- Targeting cancer stem cell pathways for cancer therapy.Signal transduction and targeted therapy · 2020Review
- Inhibition of mutant PPM1D enhances DNA damage response and growth suppressive effects of ionizing radiation in diffuse intrinsic pontine glioma.Neuro-oncology · 2019Article
- p53 Function Is Compromised by Inhibitor 2 of Phosphatase 2A in Sonic Hedgehog Medulloblastoma.Molecular cancer research : MCR · 2019Article
- Non-canonical Hedgehog Signaling Pathway in Cancer: Activation of GLI Transcription Factors Beyond Smoothened.Frontiers in genetics · 2019Review
- Emerging Roles of Sonic Hedgehog in Adult Neurological Diseases: Neurogenesis and Beyond.International journal of molecular sciences · 2018Review
- Medulloblastoma, WNT-activated/SHH-activated: clinical impact of molecular analysis and histogenetic evaluation.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2018Review
- Hedgehog signaling in the stomach.Current opinion in pharmacology · 2016Review
- ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
High-level amplification of the protein phosphatase PPM1D (WIP1) is present in a subset of medulloblastomas (MBs) that have an expression profile consistent with active Sonic Hedgehog (SHH) signaling. We found that WIP1 overexpression increased expression of Shh target genes and cell proliferation in response to Shh stimulation in NIH3T3 and cerebellar granule neuron precursor cells in a p53-independent manner. Thus, we developed a mouse in which WIP1 is expressed in the developing brain under control of the Neurod2 promoter (ND2:WIP1). The external granule layer (EGL) in early postnatal ND2:WIP1 mice exhibited increased proliferation and expression of Shh downstream targets. MB incidence increased and survival decreased when ND2:WIP1 mice were crossed with an Shh-activated MB mouse model. Conversely, Wip1 knockout significantly suppressed MB formation in two independent mouse models of Shh-activated MB. Furthermore, Wip1 knockdown or treatment with a WIP1 inhibitor suppressed the effects of Shh stimulation and potentiated the growth inhibitory effects of SHH pathway-inhibiting drugs in Shh-activated MB cells in vitro. This suggests an important cross-talk between SHH and WIP1 pathways that accelerates tumorigenesis and supports WIP1 inhibition as a potential treatment strategy for MB.
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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.