ArticleNature communications2021
Protein phosphatase 2A inactivation induces microsatellite instability, neoantigen production and immune response.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
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- Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer (NECTAR): a multi-center phase 2 study.Signal transduction and targeted therapy · 2024Trial
- CEST-MRI assessment of locally advanced pMMR rectal cancer for prediction of immune activation status following radiotherapy.European radiology · 2026Article
- Phenotypic Analysis of Mice with Conditional Knockout of PPP2CA in Colonic Tissues.Digestive diseases and sciences · 2026Article
- Protein phosphatase 2A regulates senescence and immunogenicity in medulloblastoma models.The Journal of clinical investigation · 2026Article
- 10-Hydroxy-2-decenoic Acid Suppresses Colorectal Cancer Progression by Inhibiting Wnt/β-Catenin Signaling and Promoting Apoptosis.Foods (Basel, Switzerland) · 2026Article
- Unlocking Wnt's weak spot: Glycosylated nanoalbumins to reignite immune responses in MSS-CRC.Journal of pharmaceutical analysis · 2026Article
- Molecular origin, discovery, validation and application of neoantigens.Asian journal of pharmaceutical sciences · 2026Review
- Identification of lncRNAs Indicating Immune Pathway Activity for Predicting Prognosis and Immunotherapy Response in Pan-Cancer.Cancer medicine · 2026Article
- On the history, synthesis, and medicinal use of cantharidin, LB-100, and their analogs.RSC medicinal chemistry · 2026Review
- Post-translational modifications in retinoblastoma: mechanisms, immune regulation, and therapeutic opportunities.Frontiers in immunology · 2026Review
- Immune checkpoint inhibitors in dMMR-MSI-H colorectal cancer: rationale, progress and prospects.Frontiers in immunology · 2026Review
- Integrated bioinformatics analysis identifies RPS27A and PPP2R1A as shared hub genes in heart failure and COVID-19.Journal of cardiothoracic surgery · 2025Article
- A single gene mutation predicts response to immune checkpoint blockade in ovarian clear cell carcinoma.Molecular oncology · 2025Article
- Article
- Proteomics in pancreatic cancer.Biomarker research · 2025Review
- PRMT5 Inhibitor Synergizes with Chemotherapy to Induce Resembling Mismatch Repair Deficiency and Enhance Anti-TIGIT Therapy in Microsatellite-Stable Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Cancer stem cells and niches: challenges in immunotherapy resistance.Molecular cancer · 2025Review
- IDO1 inhibitor enhances the effectiveness of PD-1 blockade in microsatellite stable colorectal cancer by promoting macrophage pro-inflammatory phenotype polarization.Cancer immunology, immunotherapy : CII · 2025Article
- Influence of Immunoexpression of Mismatch Repair Complex Proteins on Disease-Free Survival in Non-Surgically Treated Oropharyngeal Squamous Cell Carcinomas.Head and neck pathology · 2024Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Microsatellite-instable (MSI), a predictive biomarker for immune checkpoint blockade (ICB) response, is caused by mismatch repair deficiency (MMRd) that occurs through genetic or epigenetic silencing of MMR genes. Here, we report a mechanism of MMRd and demonstrate that protein phosphatase 2A (PP2A) deletion or inactivation converts cold microsatellite-stable (MSS) into MSI tumours through two orthogonal pathways: (i) by increasing retinoblastoma protein phosphorylation that leads to E2F and DNMT3A/3B expression with subsequent DNA methylation, and (ii) by increasing histone deacetylase (HDAC)2 phosphorylation that subsequently decreases H3K9ac levels and histone acetylation, which induces epigenetic silencing of MLH1. In mouse models of MSS and MSI colorectal cancers, triple-negative breast cancer and pancreatic cancer, PP2A inhibition triggers neoantigen production, cytotoxic T cell infiltration and ICB sensitization. Human cancer cell lines and tissue array effectively confirm these signaling pathways. These data indicate the dual involvement of PP2A inactivation in silencing MLH1 and inducing MSI.
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