ArticleOncotarget2016
Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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Who cites it
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- The role of PPM1D in cancer and advances in studies of its inhibitors.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2020Pooled it
- Molecular landscape and clinical translation of DNA damage response alterations in solid tumors: A pan-cancer perspective on precision oncology.Neoplasia (New York, N.Y.) · 2026Review
- Combined inhibition of PLK4 and PPM1D promotes cell death in cancer cells with 17q amplification.Cancer cell international · 2026Article
- KDM4D enhances radiosensitivity in esophageal squamous cell carcinoma through the SRBD1/RPL11/c-Myc/WIP1/CHK1 axis.American journal of translational research · 2026Article
- PPM1D is directly degraded by proteasomes in a ubiquitination-independent manner through its carboxyl-terminal region.Journal of biomedical science · 2025Article
- Cell confluency affects p53 dynamics in response to DNA damage.Molecular biology of the cell · 2025Article
- Targeted inhibition of WIP1 and histone H3K27 demethylase activity synergistically suppresses neuroblastoma growth.Cell death & disease · 2025Article
- Identification of small molecule inhibitors of PPM1D using an integrated drug discovery platform.iScience · 2025Article
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- PPM1D/Wip1 is amplified, overexpressed, and mutated in human non-Hodgkin's lymphomas.Molecular biology reports · 2024Article
- PPM1D activity promotes cellular transformation by preventing senescence and cell death.Oncogene · 2024Article
- Identification of Small Molecule Inhibitors of PPM1D Using a Novel Drug Discovery Platform.bioRxiv : the preprint server for biology · 2024Article
- Review
- PPM1D activity promotes the replication stress caused by cyclin E1 overexpression.Molecular oncology · 2024Article
- Wip1 inhibits neutrophil extracellular traps to promote abscess formation in mice by directly dephosphorylating Coronin-1a.Cellular & molecular immunology · 2023Article
- 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
- Phosphorylation of TRF2 promotes its interaction with TIN2 and regulates DNA damage response at telomeres.Nucleic acids research · 2023Article
- Phosphoproteomic analysis of metformin signaling in colorectal cancer cells elucidates mechanism of action and potential therapeutic opportunities.Clinical and translational medicine · 2023Article
- miR-16-5p enhances sensitivity to RG7388 through targetingCancer drug resistance (Alhambra, Calif.) · 2023Article
- PPM1D suppresses p53-dependent transactivation and cell death by inhibiting the Integrated Stress Response.Nature communications · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
PP2C family serine/threonine phosphatase WIP1 acts as a negative regulator of the tumor suppressor p53 and is implicated in silencing of cellular responses to genotoxic stress. Chromosomal locus 17q23 carrying the PPM1D (coding for WIP1) is commonly amplified in breast carcinomas and WIP1 was proposed as potential pharmacological target. Here we employed a cellular model with knocked out PPM1D to validate the specificity and efficiency of GSK2830371, novel small molecule inhibitor of WIP1. We have found that GSK2830371 increased activation of the DNA damage response pathway to a comparable level as the loss of PPM1D. In addition, GSK2830371 did not affect proliferation of cells lacking PPM1D but significantly supressed proliferation of breast cancer cells with amplified PPM1D. Over time cells treated with GSK2830371 accumulated in G1 and G2 phases of the cell cycle in a p21-dependent manner and were prone to induction of senescence by a low dose of MDM2 antagonist nutlin-3. In addition, combined treatment with GSK2830371 and doxorubicin or nutlin-3 potentiated cell death through a strong induction of p53 pathway and activation of caspase 9. We conclude that efficient inhibition of WIP1 by GSK2830371 sensitizes breast cancer cells with amplified PPM1D and wild type p53 to chemotherapy.
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