ArticleThe Journal of experimental medicine2012
Vital roles of mTOR complex 2 in Notch-driven thymocyte differentiation and leukemia.
Article in The Journal of experimental medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
What it found
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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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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Not only a therapeutic target; mTOR in Hodgkin lymphoma and acute lymphoblastic leukemia.Frontiers in oncology · 2024Pooled it
- PTEN-mTORC2 signaling module controls antibody isotype selection and antiviral humoral immunity.Frontiers in immunology · 2026Article
- Food for thought: Nutrient metabolism controlling early T cell development.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.Journal of endocrinological investigation · 2024Article
- MicroRNAs targeted mTOR as therapeutic agents to improve radiotherapy outcome.Cancer cell international · 2024Review
- Plasma Cell Differentiation, Antibody Quality, and Initial Germinal Center B Cell Population Depend on Glucose Influx Rate.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Hypoxia and the Hypoxia-Inducible Factors in Lymphocyte Differentiation and Function.Advances in experimental medicine and biology · 2024Review
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- mTORC1 Deficiency Prevents the Development of MC903-Induced Atopic Dermatitis through the Downregulation of Type 2 Inflammation.International journal of molecular sciences · 2023Article
- The progress of autoimmune hepatitis research and future challenges.Open medicine (Warsaw, Poland) · 2023Review
- Dietary glucosamine overcomes the defects in αβ-T cell ontogeny caused by the loss of de novo hexosamine biosynthesis.Nature communications · 2022Article
- C-C Chemokine Receptor 7 in Cancer.Cells · 2022Review
- Metabolic regulation of T cell development.Frontiers in immunology · 2022Review
- Review
- New Insights into the Pathogenesis of Systemic Mastocytosis.International journal of molecular sciences · 2021Review
- mTOR-targeted cancer therapy: great target but disappointing clinical outcomes, why?Frontiers of medicine · 2021Review
- Expanding TOR Complex 2 Signaling: Emerging Regulators and New Connections.Frontiers in cell and developmental biology · 2021Review
- CCR7 in Blood Cancers - Review of Its Pathophysiological Roles and the Potential as a Therapeutic Target.Frontiers in oncology · 2021Review
- Searching for the real function of mTOR signaling in the regulation of PD-L1 expression.Translational oncology · 2020Review
- A phase I study of a dual PI3-kinase/mTOR inhibitor BEZ235 in adult patients with relapsed or refractory acute leukemia.BMC pharmacology & toxicology · 2020Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Notch plays critical roles in both cell fate decisions and tumorigenesis. Notch receptor engagement initiates signaling cascades that include a phosphatidylinositol 3-kinase/target of rapamycin (TOR) pathway. Mammalian TOR (mTOR) participates in two distinct biochemical complexes, mTORC1 and mTORC2, and the relationship between mTORC2 and physiological outcomes dependent on Notch signaling is unknown. In this study, we report contributions of mTORC2 to thymic T-cell acute lymphoblastic leukemia (T-ALL) driven by Notch. Conditional deletion of Rictor, an essential component of mTORC2, impaired Notch-driven proliferation and differentiation of pre-T cells. Furthermore, NF-κB activity depended on the integrity of mTORC2 in thymocytes. Active Akt restored NF-κB activation, a normal rate of proliferation, and differentiation of Rictor-deficient pre-T cells. Strikingly, mTORC2 depletion lowered CCR7 expression in thymocytes and leukemic cells, accompanied by decreased tissue invasion and delayed mortality in T-ALL driven by Notch. Collectively, these findings reveal roles for mTORC2 in promoting thymic T cell development and T-ALL and indicate that mTORC2 is crucial for Notch signaling to regulate Akt and NF-κB.
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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.