ArticleOncogene2018
Loss of protein phosphatase 2A regulatory subunit B56δ promotes spontaneous tumorigenesis in vivo.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Protein phosphatase 2 phosphatase activator (PTPA) promotes oncogene-induced senescence and carboplatin response in human malignant pleural mesothelioma cells.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- Germline mutations in PPP2R1B in patients with a personal and family history of cancer.JCI insight · 2025Article
- Pathogenic de novo variants in PPP2R5C cause a neurodevelopmental disorder within the Houge-Janssens syndrome spectrum.American journal of human genetics · 2025Article
- A de novo missense mutation in PPP2R5D alters dopamine pathways and morphology of iPSC-derived midbrain neurons.Stem cells (Dayton, Ohio) · 2025Article
- Unmasking Protein Phosphatase 2A Regulatory Subunit B as a Crucial Factor in the Progression of Dilated Cardiomyopathy.Biomedicines · 2024Article
- Concomitant targeting of FLT3 and SPHK1 exerts synergistic cytotoxicity in FLT3-ITDCell communication and signaling : CCS · 2024Article
- Emerging Roles of B56 Phosphorylation and Binding Motif in PP2A-B56 Holoenzyme Biological Function.International journal of molecular sciences · 2024Review
- B56δ long-disordered arms form a dynamic PP2A regulation interface coupled with global allostery and Jordan's syndrome mutations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss ofCancers · 2023Article
- Extended regulation interface coupled to the allosteric network and disease mutations in the PP2A-B56δ holoenzyme.bioRxiv : the preprint server for biology · 2023Article
- Structural mechanism for inhibition of PP2A-B56α and oncogenicity by CIP2A.Nature communications · 2023Article
- 2D-DIGE Analysis of Liver Disease in Mice.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Target c-Myc to treat pancreatic cancer.Cancer biology & therapy · 2022Article
- The Pivotal Role of Protein Phosphatase 2A (PP2A) in Brain Tumors.International journal of molecular sciences · 2022Review
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- PPP2R5D promotes hepatitis C virus infection by binding to viral NS5B and enhancing viral RNA replication.Virology journal · 2022Article
- Review
- Growth arrest of PPP2R5C and PPP2R5D double knockout mice indicates a genetic interaction and conserved function for these PP2A B subunits.FASEB bioAdvances · 2022Article
- IGFBP-3 and TGF-β inhibit growth in epithelial cells by stimulating type V TGF-β receptor (TβR-V)-mediated tumor suppressor signaling.FASEB bioAdvances · 2021Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protein Phosphatase 2A (PP2A) enzymes counteract diverse kinase-driven oncogenic pathways and their function is frequently impaired in cancer. PP2A inhibition is indispensable for full transformation of human cells, but whether loss of PP2A is sufficient for tumorigenesis in vivo has remained elusive. Here, we describe spontaneous tumor development in knockout mice for Ppp2r5d, encoding the PP2A regulatory B56δ subunit. Several primary tumors were observed, most commonly, hematologic malignancies and hepatocellular carcinomas (HCCs). Targeted immunoblot and immunohistochemistry analysis of the HCCs revealed heterogeneous activation of diverse oncogenic pathways known to be suppressed by PP2A-B56. RNA sequencing analysis unveiled, however, a common role for oncogenic c-Myc activation in the HCCs, independently underscored by c-Myc Ser62 hyperphosphorylation. Upstream of c-Myc, GSK-3β Ser9 hyperphosphorylation occurred both in the HCCs and non-cancerous B56δ-null livers. Thus, uncontrolled c-Myc activity due to B56δ-driven GSK-3β inactivation is the likely tumor predisposing factor. Our data provide the first compelling mouse genetics evidence sustaining the tumor suppressive activity of a single PP2A holoenzyme, constituting the final missing incentive for full clinical development of PP2A as cancer biomarker and therapy target.
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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.