ArticlePloS one2013
MEK/ERK dependent activation of STAT1 mediates dasatinib-induced differentiation of acute myeloid leukemia.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Trial
- Adding dasatinib to intensive treatment in core-binding factor acute myeloid leukemia-results of the AMLSG 11-08 trial.Leukemia · 2018Trial
- Article
- Comprehensive Insight into the Functional Roles of NK and NKT Cells in HTLV-1-Associated Diseases and Asymptomatic Carriers.Molecular neurobiology · 2024Review
- Dasatinib in core-binding factor acute myeloid leukemia: A promising therapeutic approach.EJHaem · 2024Article
- Inhibition of Extracellular Signal-Regulated Kinase Activity Improves Cognitive Function in Mice Subjected to Myocardial Infarction.Cardiovascular toxicology · 2024Article
- Inhibition of CDKL3 downregulates STAT1 thus suppressing prostate cancer development.Cell death & disease · 2023Article
- Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.EMBO molecular medicine · 2023Article
- Cytomegalovirus US28 regulates cellular EphA2 to maintain viral latency.Science advances · 2022Article
- Article
- 2-Hydroxyestradiol Overcomes Mesenchymal Stem Cells-Mediated Platinum Chemoresistance in Ovarian Cancer Cells in an ERK-Independent Fashion.Molecules (Basel, Switzerland) · 2022Article
- PKD3 promotes metastasis and growth of oral squamous cell carcinoma through positive feedback regulation with PD-L1 and activation of ERK-STAT1/3-EMT signalling.International journal of oral science · 2021Article
- Dasatinib overcomes stroma-based resistance to the FLT3 inhibitor quizartinib using multiple mechanisms.Leukemia · 2020Article
- Leukemia Inhibitory Factor Signaling Enhances Production of Galactose-Deficient IgA1 in IgA Nephropathy.Kidney diseases (Basel, Switzerland) · 2020Article
- Protein kinase D3 regulates the expression of the immunosuppressive protein, PD‑L1, through STAT1/STAT3 signaling.International journal of oncology · 2020Article
- A Novel System for Functional Determination of Variants of Uncertain Significance using Deep Convolutional Neural Networks.Scientific reports · 2020Article
- CD97 is a critical regulator of acute myeloid leukemia stem cell function.The Journal of experimental medicine · 2019Article
- Ortho-Topolin Riboside Induced Differentiation through Inhibition of STAT3 Signaling in Acute Myeloid Leukemia HL-60 CellsTurkish journal of haematology : official journal of Turkish Society of Haematology · 2019Article
- Diptoindonesin G promotes ERK-mediated nuclear translocation of p-STAT1 (Ser727) and cell differentiation in AML cells.Cell death & disease · 2017Article
- Analysis of the interplay between all-trans retinoic acid and histone deacetylase inhibitors in leukemic cells.Archives of toxicology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dasatinib (BMS-354825) is a FDA-approved multitargeted kinase inhibitor of BCR/ABL and Src kinases. It is now used in the treatment of chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapies, including imatinib. Here we report a novel effect of dasatinib on inducing the differentiation of acute myeloid leukemia (AML) cells through MEK/ERK-dependent activation of signal transducer and activator of transcription 1 (STAT1). We found that dasatinib could induce the differentiation of AML cells as demonstrated by the expression of differentiation marker CD11b, G0/G1 phase arrest and decreased ratio of nucleus to cytoplasm. Of note, dasatinib induced robust phosphorylation of STAT1 both at Tyr701 and Ser727 as well as the redistribution of STAT1 from the cytoplasm to the nucleus, thus leading to the transcription of STAT1-targeted genes. Knocking down STAT1 expression by shRNA significantly attenuated dasatinib-induced differentiation, indicating an important role of STAT1 in myeloid maturation. We further found that dasatinib-induced activation of STAT1 was regulated by the MEK/ERK kinases. The phosporylation of MEK and ERK occurred rapidly upon dasatinib treatment and increased progressively as differentiation was induced. MEK inhibitors PD98059 and U0216 not only inhibited the phosphorylation of STAT1, but also abrogated dasatinib-induced myeloid differentiation, suggesting that MEK/ERK dependent phosphorylation of STAT1 might be indispensable for the differentiating effect of dasatinib in AML cells. Taken together, our study suggests that STAT1 is an important mediator in dasatinib-induced differentiation of AML cells, whose activation requires the activation of MEK/ERK cascades.
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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.