ArticlePloS one2015
Endothelial Cell mTOR Complex-2 Regulates Sprouting Angiogenesis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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.
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.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Incidence and predictors of hemorrhage in pediatric low-grade glioma.Journal of neuro-oncology · 2026Article
- PTBP1 supports mouse spermatogenesis by facilitating cytoskeletal organization through the mTORC2-PKCα pathway in Sertoli cells.Communications biology · 2026Article
- Polyploidy and Senescence of Cancer Cells: Impact of Cell Fusion.Advances in experimental medicine and biology · 2026Review
- Cell communication and relevant signaling pathways in osteogenesis-angiogenesis coupling.Bone research · 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
- Veratridine, a plant-derived alkaloid, suppresses the hyperactive Rictor-mTORC2 pathway: a new targeted therapy for primary and metastatic colorectal cancer.Research square · 2024Article
- Schizophrenia endothelial cells exhibit higher permeability and altered angiogenesis patterns in patient-derived organoids.Translational psychiatry · 2024Article
- UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.Oncogene · 2023Article
- Targeting mTOR for Anti-Aging and Anti-Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Inhibitory effect of ginsenglactone A fromJournal of ginseng research · 2023Article
- Microphysiological model of PIK3CA-driven vascular malformations reveals a role of dysregulated Rac1 and mTORC1/2 in lesion formation.Science advances · 2023Article
- Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis.Nature communications · 2022Article
- Protrudin regulates FAK activation, endothelial cell migration and angiogenesis.Cellular and molecular life sciences : CMLS · 2022Article
- CFTR limits F-actin formation and promotes morphological alignment with flow in human lung microvascular endothelial cells.Physiological reports · 2021Article
- Translational control in neurovascular brain development.Royal Society open science · 2021Review
- Synapomorphic features of hepatic and pulmonary vasculatures include comparable purinergic signaling responses in host defense and modulation of inflammation.American journal of physiology. Gastrointestinal and liver physiology · 2021Review
- Mechanistic Target of Rapamycin Complex 2 Regulation of the Primary Human Trophoblast Cell Transcriptome.Frontiers in cell and developmental biology · 2021Article
- Mendelian randomization and experimental IUGR reveal the adverse effect of low birth weight on lung structure and function.Scientific reports · 2020Article
- Ras, PI3K and mTORC2 - three's a crowd?Journal of cell science · 2020Review
- Loss of S6K1 But Not S6K2 in the Tumor Microenvironment Suppresses Tumor Growth by Attenuating Tumor Angiogenesis.Translational oncology · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tumor neovascularization is targeted by inhibition of vascular endothelial growth factor (VEGF) or the receptor to prevent tumor growth, but drug resistance to angiogenesis inhibition limits clinical efficacy. Inhibition of the phosphoinositide 3 kinase pathway intermediate, mammalian target of rapamycin (mTOR), also inhibits tumor growth and may prevent escape from VEGF receptor inhibitors. mTOR is assembled into two separate multi-molecular complexes, mTORC1 and mTORC2. The direct effect of mTORC2 inhibition on the endothelium and tumor angiogenesis is poorly defined. We used pharmacological inhibitors and RNA interference to determine the function of mTORC2 versus Akt1 and mTORC1 in human endothelial cells (EC). Angiogenic sprouting, EC migration, cytoskeleton re-organization, and signaling events regulating matrix adhesion were studied. Sustained inactivation of mTORC1 activity up-regulated mTORC2-dependent Akt1 activation. In turn, ECs exposed to mTORC1-inhibition were resistant to apoptosis and hyper-responsive to renal cell carcinoma (RCC)-stimulated angiogenesis after relief of the inhibition. Conversely, mTORC1/2 dual inhibition or selective mTORC2 inactivation inhibited angiogenesis in response to RCC cells and VEGF. mTORC2-inactivation decreased EC migration more than Akt1- or mTORC1-inactivation. Mechanistically, mTORC2 inactivation robustly suppressed VEGF-stimulated EC actin polymerization, and inhibited focal adhesion formation and activation of focal adhesion kinase, independent of Akt1. Endothelial mTORC2 regulates angiogenesis, in part by regulation of EC focal adhesion kinase activity, matrix adhesion, and cytoskeletal remodeling, independent of Akt/mTORC1.
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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.