ArticleOncotarget2016
Combined targeting of SET and tyrosine kinases provides an effective therapeutic approach in human T-cell acute lymphoblastic leukemia.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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
15 citing papers in PubMed, 32 citations in OpenAlex.
- The next decade of SET: from an oncoprotein to beyond.Journal of molecular cell biology · 2024Review
- PP2A-based triple-strike therapy overcomes mitochondrial apoptosis resistance in brain cancer cells.Molecular oncology · 2023Article
- The Effects of Protein Phosphatase 2A Activation with Novel Tricyclic Sulfonamides on Hepatoblastoma.Journal of pediatric surgery · 2023Article
- Thirty years of SET/TAF1β/I2PP2A: from the identification of the biological functions to its implications in cancer and Alzheimer's disease.Bioscience reports · 2022Review
- PPP2CA Is a Novel Therapeutic Target in Neuroblastoma Cells That Can Be Activated by the SET Inhibitor OP449.Frontiers in oncology · 2022Article
- SET levels contribute to cohesion fatigue.Molecular biology of the cell · 2021Article
- PP2A-activating Drugs Enhance FLT3 Inhibitor Efficacy through AKT Inhibition-Dependent GSK-3β-Mediated c-Myc and Pim-1 Proteasomal Degradation.Molecular cancer therapeutics · 2021Article
- Antileukemic efficacy of a potent artemisinin combined with sorafenib and venetoclax.Blood advances · 2021Article
- Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1.The Journal of biological chemistry · 2020Article
- Review
- Protein phosphatase 2A activation as a therapeutic strategy for managing MYC-driven cancers.The Journal of biological chemistry · 2020Article
- Redox inhibition of protein phosphatase PP2A: Potential implications in oncogenesis and its progression.Redox biology · 2019Review
- Protein phosphatase 2A as a therapeutic target in inflammation and neurodegeneration.Pharmacology & therapeutics · 2019Review
- Matrine induced G0/G1 arrest and apoptosis in human acute T-cell lymphoblastic leukemia (T-ALL) cells.Bosnian journal of basic medical sciences · 2018Article
- Patients over 40 years old with precursor T-cell lymphoblastic lymphoma have different prognostic factors comparing to the youngers.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Recent evidence suggests that inhibition of protein phosphatase 2A (PP2A) tumor suppressor activity via the SET oncoprotein contributes to the pathogenesis of various cancers. Here we demonstrate that both SET and c-MYC expression are frequently elevated in T-ALL cell lines and primary samples compared to healthy T cells. Treatment of T-ALL cells with the SET antagonist OP449 restored the activity of PP2A and reduced SET interaction with the PP2A catalytic subunit, resulting in a decrease in cell viability and c-MYC expression in a dose-dependent manner. Since a tight balance between phosphatases and kinases is required for the growth of both normal and malignant cells, we sought to identify a kinase inhibitor that would synergize with SET antagonism. We tested various T-ALL cell lines against a small-molecule inhibitor screen of 66 compounds targeting two-thirds of the tyrosine kinome and found that combined treatment of T-ALL cells with dovitinib, an orally active multi-targeted small-molecule receptor tyrosine kinase inhibitor, and OP449 synergistically reduced the viability of all tested T-ALL cell lines. Mechanistically, combined treatment with OP449 and dovitinib decreased total and phospho c-MYC levels and reduced ERK1/2, AKT, and p70S6 kinase activity in both NOTCH-dependent and independent T-ALL cell lines. Overall, these results suggest that combined targeting of tyrosine kinases and activation of serine/threonine phosphatases may offer novel therapeutic strategies for the treatment of T-ALL.
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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.