ArticleOncotarget2016
IRS2 silencing increases apoptosis and potentiates the effects of ruxolitinib in JAK2V617F-positive myeloproliferative neoplasms.
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.
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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, 25 citations in OpenAlex.
- Obesity and Leukemia: Biological Mechanisms, Perspectives, and Challenges.Current obesity reports · 2024Review
- Molecular Genetics of Thrombotic Myeloproliferative Neoplasms: Implications in Precision Oncology.Diagnostics (Basel, Switzerland) · 2023Review
- Regulation of erythroid differentiation in K562 cells by the EPAS1-IRS2 axis under hypoxic conditions.Frontiers in cell and developmental biology · 2023Article
- Article
- Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands.Journal of medicinal chemistry · 2022Article
- MicroRNAs as the critical regulators of cell migration and invasion in thyroid cancer.Biomarker research · 2022Review
- Insights into the Potential Mechanisms of JAK2V617F Somatic Mutation Contributing Distinct Phenotypes in Myeloproliferative Neoplasms.International journal of molecular sciences · 2022Review
- MPA alters metabolic phenotype of endometrial cancer-associated fibroblasts from obese women via IRS2 signaling.PloS one · 2022Article
- Novel agents for the treatment of polycythemia vera: an insight into preclinical research and early phase clinical trials.Expert opinion on investigational drugs · 2020Review
- NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2Signal transduction and targeted therapy · 2020Article
- Insulin Substrate Receptor (IRS) proteins in normal and malignant hematopoiesis.Clinics (Sao Paulo, Brazil) · 2018Review
- IL-4 and IL-13 Receptor Signaling From 4PS to Insulin Receptor Substrate 2: There and Back Again, a Historical View.Frontiers in immunology · 2018Review
- MiR-338-3p inhibits the growth and invasion of non-small cell lung cancer cells by targeting IRS2.American journal of cancer research · 2017Article
- Systems analysis uncovers inflammatory Th/Tc17-driven modules during acute GVHD in monkey and human T cells.Blood · 2016Article
- microRNA-141 inhibits thyroid cancer cell growth and metastasis by targeting insulin receptor substrate 2.American journal of translational research · 2016Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
The recurrent V617F mutation in JAK2 (JAK2V617F) has emerged as the primary contributor to the pathogenesis of myeloproliferative neoplasms (MPN). However, the lack of complete response in most patients treated with the JAK1/2 inhibitor, ruxolitinib, indicates the need for identifying pathways that cooperate with JAK2. Activated JAK2 was found to be associated with the insulin receptor substrate 2 (IRS2) in non-hematological cells. We identified JAK2/IRS2 binding in JAK2V617F HEL cells, but not in the JAK2WT U937 cell line. In HEL cells, IRS2 silencing decreased STAT5 phosphorylation, reduced cell viability and increased apoptosis; these effects were enhanced when IRS2 silencing was combined with ruxolitinib. In U937 cells, IRS2 silencing neither reduced cell viability nor induced apoptosis. IRS1/2 pharmacological inhibition in primary MPN samples reduced cell viability in JAK2V617F-positive but not JAK2WT specimens; combination with ruxolitinib had additive effects. IRS2 expression was significantly higher in CD34+ cells from essential thrombocythemia patients compared to healthy donors, and in JAK2V617F MPN patients when compared to JAK2WT. Our data indicate that IRS2 is a binding partner of JAK2V617F in MPN. IRS2 contributes to increased cell viability and reduced apoptosis in JAK2-mutated cells. Combined pharmacological inhibition of IRS2 and JAK2 may have a potential clinical application in MPN.
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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.