ArticleJournal of hematology & oncology2016
Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia.
Article in Journal of hematology & oncology, 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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Who cites it
21 citing papers in PubMed, 27 citations in OpenAlex.
- Selective non-nuclear estrogen receptor activation with PaPE-1 evokes neuroprotection involving mTOR/MEK in an in vitro model of hypoxic/ischemic injury.Pharmacological reports : PR · 2026Article
- Regulatory role of mTORC1 signaling in osteoblasts in acute myeloid leukemia progression and steady-state hematopoiesis.iScience · 2026Article
- mTOR signaling networks: mechanistic insights and translational frontiers in disease therapeutics.Signal transduction and targeted therapy · 2025Review
- Constitutive activation of the Src-family kinases Fgr and Hck enhances the tumor burden of acute myeloid leukemia cells in immunocompromised mice.Scientific reports · 2025Article
- ZNPs reduce epidermal mechanical strain resistance by promoting desmosomal cadherin endocytosis via mTORC1-TFEB-BLOC1S3 axis.Journal of nanobiotechnology · 2024Article
- Loss of RNA-binding protein CELF2 promotes acute leukemia development via FAT10-mTORC1.Oncogene · 2024Article
- The occurrence and development of induced pluripotent stem cells.Frontiers in genetics · 2024Review
- Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease.Signal transduction and targeted therapy · 2023Review
- Article
- Cardio-Onco-Metabolism - Metabolic vulnerabilities in cancer and the heart.Journal of molecular and cellular cardiology · 2022Review
- Adaptive responses toProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- Autophagy and apoptosis induction by sesamin in MOLT-4 and NB4 leukemia cells.Oncology letters · 2021Article
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- Tuning mTORC1 activity dictates the response of acute myeloid leukemia to LSD1 inhibition.Haematologica · 2020Article
- Rheb1 protects against cisplatin-induced tubular cell death and acute kidney injury via maintaining mitochondrial homeostasis.Cell death & disease · 2020Article
- Nanotechnology-Based Targeting of mTOR Signaling in Cancer.International journal of nanomedicine · 2020Review
- Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019Review
- Role of mTORC1-S6K1 signaling pathway in regulation of hematopoietic stem cell and acute myeloid leukemia.Experimental hematology · 2017Review
- New tricks for human farnesyltransferase inhibitor: cancer and beyond.MedChemComm · 2017Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link between PI3K/Akt and mTOR kinase, the role of Rheb1 in AML remains unexplored. Our study aims to explore the role of Rheb1 in AML and estimate whether Rheb1 could be a potential target of AML treatment.
methodsThe expressions of Rheb1 and other indicated genes were analyzed using real-time PCR. AML mouse model was established by retrovirus transduction. Leukemia cell properties and related signaling pathways were dissected by in vitro and in vivo studies. The transcriptional changes were analyzed via gene chip analysis. Molecular reagents including mTOR inhibitor and mTOR activator were used to evaluate the function of related signaling pathway in the mouse model.
resultsWe observed that Rheb1 is overexpressed in AML patients and the change of Rheb1 level in AML patients is associated with their median survival. Using a Rheb1-deficient MLL-AF9 murine AML model, we revealed that Rheb1 deletion prolonged the survival of AML mice by weakening LSC function. In addition, Rheb1 deletion arrested cell cycle progression and enhanced apoptosis of AML cells. Furthermore, while Rheb1 deletion reduced mTORC1 activity in AML cells, additional rapamycin treatment further decreased mTORC1 activity and increased the apoptosis of Rheb1 (Δ/Δ) AML cells. The mTOR activator 3BDO partially rescued mTORC1 signaling and inhibited apoptosis in Rheb1 (Δ/Δ) AML cells.
conclusionsOur data suggest that Rheb1 promotes AML progression through mTORC1 signaling pathway and combinational drug treatments targeting Rheb1 and mTOR might have a better therapeutic effect on leukemia.
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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.