ArticleOncogene2020
Inactivation of PP2A by a recurrent mutation drives resistance to MEK inhibitors.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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.
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
30 citing papers in PubMed, 47 citations in OpenAlex.
- The role of PPP2R1A variants in gynecologic malignancies: a paradigm shift in immuno-oncology.Journal of translational medicine · 2026Review
- Small Molecule Activator of Phosphatase PP2A Remodels Scaffold PR65 Structural Dynamics To Promote Holoenzyme Assembly.JACS Au · 2026Article
- Small molecule activator of phosphatase PP2A remodels scaffold PR65 structural dynamics to promote holoenzyme assembly.bioRxiv : the preprint server for biology · 2025Article
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- Regulatory mechanisms of PP2A complex assembly driven by physicochemical differences in A-subunit isoforms.Structure (London, England : 1993) · 2025Article
- Germline mutations in PPP2R1B in patients with a personal and family history of cancer.JCI insight · 2025Article
- Article
- STK39 inhibits antiviral immune response by inhibiting DCAF1-mediated PP2A degradation.Acta pharmaceutica Sinica. B · 2025Article
- Mutant PP2A Induces IGFBP2 Secretion to Promote Development of High-Grade Uterine Cancer.Cancer research · 2025Article
- Functional Role of Protein Phosphatase-6 (Current medicinal chemistry · 2025Review
- Review
- The PPP2R1A cancer hotspot mutant p.R183W increases clofarabine resistance in uterine serous carcinoma cells by a gain-of-function mechanism.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- PP2A B55α inhibits epithelial-mesenchymal transition via regulation of Slug expression in non-small cell lung cancer.Cancer letters · 2024Article
- Influence of point mutations on PR65 conformational adaptability: Insights from molecular simulations and nanoaperture optical tweezers.Science advances · 2024Article
- PPP2R1A regulates migration persistence through the NHSL1-containing WAVE Shell Complex.Nature communications · 2023Article
- Genomic regulation of transcription and RNA processing by the multitasking Integrator complex.Nature reviews. Molecular cell biology · 2023Review
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Mapping oncogenic protein interactions for precision medicine.International journal of cancer · 2022Review
- Article
- Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma.Cancer research · 2022Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
The serine/threonine Protein Phosphatase 2A (PP2A) functions as a tumor suppressor by negatively regulating multiple oncogenic signaling pathways. The canonical PP2A holoenzyme comprises a scaffolding subunit (PP2A Aα/β), which serves as the platform for binding of both the catalytic C subunit and one regulatory B subunit. Somatic heterozygous missense mutations in PPP2R1A, the gene encoding the PP2A Aα scaffolding subunit, have been identified across multiple cancer types, but the effects of the most commonly mutated residue, Arg-183, on PP2A function have yet to be fully elucidated. In this study, we used a series of cellular and in vivo models and discovered that the most frequent Aα R183W mutation formed alternative holoenzymes by binding of different PP2A regulatory subunits compared with wild-type Aα, suggesting a rededication of PP2A functions. Unlike wild-type Aα, which suppressed tumorigenesis, the R183W mutant failed to suppress tumor growth in vivo through activation of the MAPK pathway in RAS-mutant transformed cells. Furthermore, cells expressing R183W were less sensitive to MEK inhibitors. Taken together, our results demonstrate that the R183W mutation in PP2A Aα scaffold abrogates the tumor suppressive actions of PP2A, thereby potentiating oncogenic signaling and reducing drug sensitivity of RAS-mutant cells.
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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.