ArticleMolecular and cellular biology2011
mTORC2 is required for proliferation and survival of TSC2-null cells.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02061397 (The Safety of Simvastatin), which is not on this map. Cited by 81 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The Safety of Simvastatin (SOS) in Patients With Pulmonary Lymphangioleiomyomatosis (LAM) and With Tuberous Sclerosis Complex (TSC)
Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- A Systematic Review of Lymphangioleiomyomatosis on Diagnosis and Molecular Mechanism.BioMed research international · 2021Pooled it
- Emerging Concepts in Pathogenesis, Multiomics Applications, and Clinical Research in Lymphangioleiomyomatosis.Seminars in respiratory and critical care medicine · 2025Review
- Differential expression of PPARγ by pioglitazone and telmisartan causes effect of disparity on mTORC2-mediated cell proliferation and migration.Scientific reports · 2025Article
- Novel treatment strategies for lymphangioleiomyomatosis: a narrative review.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Class III Phosphatidylinositol-3 Kinase/Vacuolar Protein Sorting 34 in Cardiovascular Health and Disease.Journal of cardiovascular translational research · 2025Review
- Autophagy as a potential therapeutic target in regulating improper cellular proliferation.Frontiers in pharmacology · 2025Review
- Unveiling the Role of Mechanistic Target of Rapamycin Kinase (MTOR) Signaling in Cancer Progression and the Emergence of MTOR Inhibitors as Therapeutic Strategies.ACS pharmacology & translational science · 2024Review
- Plasmacytoid Dendritic Cells Mediate CpG-ODN-induced Increase in Survival in a Mouse Model of Lymphangioleiomyomatosis.American journal of respiratory cell and molecular biology · 2024Article
- Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis.bioRxiv : the preprint server for biology · 2024Article
- Anoctamin-1 is induced by TGF-β and contributes to lung myofibroblast differentiation.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Anoctamin-1 is induced by TGF-beta and contributes to lung myofibroblast differentiation.bioRxiv : the preprint server for biology · 2023Article
- Lost in translation: a neglected mTOR target for lymphangioleiomyomatosis.European respiratory review : an official journal of the European Respiratory Society · 2023Review
- An In Vitro Analysis of TKI-Based Sequence Therapy in Renal Cell Carcinoma Cell Lines.International journal of molecular sciences · 2023Article
- The role of TSC2 in breast cancer: a literature review.Frontiers in oncology · 2023Review
- Cross-talk between TSC2 and the extracellular matrix controls pulmonary vascular proliferation and pulmonary hypertension.Science signaling · 2022Article
- Proteins Associated with Phagocytosis Alteration in Retinal Pigment Epithelial Cells Derived from Age-Related Macular Degeneration Patients.Antioxidants (Basel, Switzerland) · 2022Article
- Role of PI3K-AKT-mTOR Pathway as a Pro-Survival Signaling and Resistance-Mediating Mechanism to Therapy of Prostate Cancer.International journal of molecular sciences · 2021Review
- Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration.Molecular neurodegeneration · 2021Review
- Finding new edges: systems approaches to MTOR signaling.Biochemical Society transactions · 2021Review
- CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis.International journal of molecular sciences · 2021Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Mutational inactivation of the tumor suppressor tuberous sclerosis complex 2 (TSC2) constitutively activates mTORC1, increases cell proliferation, and induces the pathological manifestations observed in tuberous sclerosis (TS) and in pulmonary lymphangioleiomyomatosis (LAM). While the role of mTORC1 in TSC2-dependent growth has been extensively characterized, little is known about the role of mTORC2. Our data demonstrate that mTORC2 modulates TSC2-null cell proliferation and survival through RhoA GTPase and Bcl2 proteins. TSC2-null cell proliferation was inhibited not only by reexpression of TSC2 or small interfering RNA (siRNA)-induced downregulation of Rheb, mTOR, or raptor, but also by siRNA for rictor. Increased RhoA GTPase activity and P-Ser473 Akt were inhibited by siRNA for rictor. Importantly, constitutively active V14RhoA reversed growth inhibition induced by siRNA for rictor, siRNA TSC1, reexpression of TSC2, or simvastatin. While siRNA for RhoA had a modest effect on growth inhibition, downregulation of RhoA markedly increased TSC2-null cell apoptosis. Inhibition of RhoA activity downregulated antiapoptotic Bcl2 and upregulated proapoptotic Bim, Bok, and Puma. In vitro and in vivo, simvastatin alone or in combination with rapamycin inhibited cell growth and induced TSC2-null cell apoptosis, abrogated TSC2-null tumor growth, improved animal survival, and prevented tumor recurrence by inhibiting cell growth and promoting apoptosis. Our data demonstrate that mTORC2-dependent activation of RhoA is required for TSC2-null cell growth and survival and suggest that targeting both mTORC2 and mTORC1 by a combination of proapoptotic simvastatin and cytostatic rapamycin shows promise for combinational therapeutic intervention in diseases with TSC2 dysfunction.
Indexed as
Identifiers
What OpenQuestion holds
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.