ArticlePloS one2017
Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 48 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
48 citing papers in PubMed, 80 citations in OpenAlex.
- JR-AB2-011 induces fast metabolic changes independent of mTOR complex 2 inhibition in human leukemia cells.Pharmacological reports : PR · 2024Article
- Modulations of the mTORC2-GATA3 axis by an isorhamnetin activated endosomal-lysosomal system of the J774.1 macrophage-like cell line.Journal of clinical biochemistry and nutrition · 2024Article
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- High-density lipoprotein protects normotensive and hypertensive rats against ischemia-reperfusion injury through differential regulation of mTORC1 and mTORC2 signaling.Frontiers in pharmacology · 2024Article
- Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.Scientific reports · 2023Article
- Somatic gain-of-function mutations in BUD13 promote oncogenesis by disrupting Fbw7 function.The Journal of experimental medicine · 2023Article
- Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2.Clinical and translational medicine · 2023Review
- Article
- Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells.Cell reports · 2023Article
- UBXN2A suppresses the Rictor-mTORC2 signaling pathway, an established tumorigenic pathway in human colorectal cancer.Oncogene · 2023Article
- Retraction: Specific blockade of Rictor-mTOR association inhibits mTORC2 activity and is cytotoxic in glioblastoma.PloS one · 2023Article
- Recent advances and limitations of mTOR inhibitors in the treatment of cancer.Cancer cell international · 2022Review
- A Tumor Suppressor Gene, N-myc Downstream-Regulated Gene 1 (NDRG1), in Gliomas and Glioblastomas.Brain sciences · 2022Review
- Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication.Frontiers in cellular and infection microbiology · 2022Article
- The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?Biomedicines · 2021Article
- Progression and metastasis of small cell lung carcinoma: the role of the PI3K/Akt/mTOR pathway and metabolic alterations.Cancer metastasis reviews · 2021Review
- Article
- TRIM28 is a transcriptional activator of the mutant TERT promoter in human bladder cancer.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Regulation of human mTOR complexes by DEPTOR.eLife · 2021Article
- mTORC2-mediated direct phosphorylation regulates YAP activity promoting glioblastoma growth and invasive characteristics.Neoplasia (New York, N.Y.) · 2021Article
Corrections and comments
- Retraction · 2023-09-08Concerns/Issues about Results and/or Conclusions · Duplication of/in Image · Error in Image · Euphemisms for Duplication · Investigation by Company/Institution · Investigation by Journal/Publisher · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · Original Data and/or Images not Provided and/or not Available · Unreliable Results and/or Conclusions · Upgrade/Update of Prior Notice(s) · · Alan Lichtenstein has VA finding of misconduct: see https://www.federalregister.gov/documents/2024/11/18/2024-26756/findings-of-research-misconduct-c;
- Correction · 2019-02-06Error in Image · Updated to Retraction · · Alan Lichtenstein has VA finding of misconduct: see https://www.federalregister.gov/documents/2024/11/18/2024-26756/findings-of-research-misconduct-c;
- Erratum issued
- Retracted
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
A small molecule which specifically blocks the interaction of Rictor and mTOR was identified utilizing a high-throughput yeast two-hybrid screen and evaluated as a potential inhibitor of mTORC2 activity in glioblastoma multiforme (GBM). In vitro, CID613034 inhibited mTORC2 kinase activity at submicromolar concentrations and in cellular assays specifically inhibited phosphorylation of mTORC2 substrates, including AKT (Ser-473), NDRG1 (Thr-346) and PKCα (Ser-657), while having no appreciable effects on the phosphorylation status of the mTORC1 substrate S6K (Thr-389) or mTORC1-dependent negative feedback loops. CID613034 demonstrated significant inhibitory effects on cell growth, motility and invasiveness in GBM cell lines and sensitivity correlated with relative Rictor or SIN1 expression. Structure-activity relationship analyses afforded an inhibitor, JR-AB2-011, with improved anti-GBM properties and blocked mTORC2 signaling and Rictor association with mTOR at lower effective concentrations. In GBM xenograft studies, JR-AB2-011 demonstrated significant anti-tumor properties. These data support mTORC2 as a viable therapeutic target in GBM and suggest that targeting protein-protein interactions critical for mTORC2 function is an effective strategy to achieve therapeutic responses.
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.