ArticleOncotarget2016
Therapeutic relevance of the protein phosphatase 2A in cancer.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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
21 citing papers in PubMed, 35 citations in OpenAlex.
- Ploidy and Implantation Potential: Non-Invasive Small Non-Coding RNA-Based Health Assessment of Day 5 and 6 Blastocysts.International journal of molecular sciences · 2025Article
- Identification of targetable vulnerabilities of PLK1-overexpressing cancers by synthetic dosage lethality.Cell genomics · 2025Article
- Identification of anoikis-related subtypes and immune landscape in kidney renal clear cell carcinoma.Scientific reports · 2023Article
- A Novel Mouse Model of Combined Hepatocellular-Cholangiocarcinoma Induced by Diethylnitrosamine and Loss ofCancers · 2023Article
- Article
- The expression profile of Gasdermin C-related genes predicts the prognosis and immunotherapy response of pancreatic adenocarcinoma.American journal of cancer research · 2023Article
- Construction of the panoptosis-related gene model and characterization of tumor microenvironment infiltration in hepatocellular carcinoma.Oncology research · 2023Article
- 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
- Grace-AKO: a novel and stable knockoff filter for variable selection incorporating gene network structures.BMC bioinformatics · 2022Article
- Bioinformatic Characterization of Whole Blood Neutrophils in Pelvic Inflammatory Disease: A Potential Prognostic Indicator for Transumbilical Single-Port Laparoscopic Pelvic Abscess Surgery.Computational and mathematical methods in medicine · 2022Article
- Highly Specific Sigma Receptor Ligands Exhibit Anti-Viral Properties in SARS-CoV-2 Infected Cells.Pathogens (Basel, Switzerland) · 2021Article
- Establishment of a Prognostic Model for Hepatocellular Carcinoma Based on Endoplasmic Reticulum Stress-Related Gene Analysis.Frontiers in oncology · 2021Article
- Detecting Chromosome Instability in Cancer: Approaches to Resolve Cell-to-Cell Heterogeneity.Cancers · 2019Review
- Targeting PP2A in cancer: Combination therapies.Biochimica et biophysica acta. Molecular cell research · 2019Review
- The Oncogenic Functions of MASTL Kinase.Frontiers in cell and developmental biology · 2018Review
- The prognostic value of Cyclin-Dependent Kinase 5 and Protein Phosphatase 2A in Gastric Cancer.Journal of Cancer · 2018Article
- Article
- Review
- Role of Protein Phosphatase 2A in Osteoblast Differentiation and Function.Journal of clinical medicine · 2017Review
Corrections and comments
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Authors and funding
27 authors at 6 institutions in 3 countries.
Funding
Abstract
Chromosomal Instability (CIN) is regarded as a unifying feature of heterogeneous tumor populations, driving intratumoral heterogeneity. Polo-Like Kinase 1 (PLK1), a serine-threonine kinase that is often overexpressed across multiple tumor types, is one of the key regulators of CIN and is considered as a potential therapeutic target. However, targeting PLK1 has remained a challenge due to the off-target effects caused by the inhibition of other members of the polo-like family. Here we use synthetic dosage lethality (SDL), where the overexpression of PLK1 is lethal only when another, normally non-lethal, mutation or deletion is present. Rather than directly inhibiting PLK1, we found that inhibition of PP2A causes selective lethality to PLK1-overexpressing breast, pancreatic, ovarian, glioblastoma, and prostate cancer cells. As PP2A is widely regarded as a tumor suppressor, we resorted to gene expression datasets from cancer patients to functionally dissect its therapeutic relevance. We identified two major classes of PP2A subunits that negatively correlated with each other. Interestingly, most mitotic regulators, including PLK1, exhibited SDL interactions with only one class of PP2A subunits (PPP2R1A, PPP2R2D, PPP2R3B, PPP2R5B and PPP2R5D). Validation studies and other functional cell-based assays showed that inhibition of PPP2R5D affects both levels of phospho-Rb as well as sister chromatid cohesion in PLK1-overexpressing cells. Finally, analysis of clinical data revealed that patients with high expression of mitotic regulators and low expression of Class I subunits of PP2A improved survival. Overall, these observations point to a context-dependent role of PP2A that warrants further exploration for therapeutic benefits.
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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.