ArticleNeuro-oncology2018
A molecular cascade modulates MAP1B and confers resistance to mTOR inhibition in human glioblastoma.
Article in Neuro-oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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.
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
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Deficiency in the Treatment Description of mTOR Inhibitor Resistance in Medulloblastoma, a Systematic Review.International journal of molecular sciences · 2021Pooled it
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- PMEnvironment & health (Washington, D.C.) · 2026Article
- Critical role of cell competition in gliomagenesis.bioRxiv : the preprint server for biology · 2026Article
- Systems Biology of Recombinant 2G12 and 353/11 mAb Production in CHO-K1 Cell Lines at Phosphoproteome Level.Proteomes · 2025Article
- Computational analysis of treatment resistant cancer cells.Frontiers in cell and developmental biology · 2025Article
- Modulation of the cytoskeleton for cancer therapy.Frontiers in cell and developmental biology · 2025Article
- FPR1 signaling aberrantly regulates S100A8/A9 production by CD14Communications biology · 2024Article
- CDK7 and CDK9 inhibition interferes with transcription, translation, and stemness, and induces cytotoxicity in GBM irrespective of temozolomide sensitivity.Neuro-oncology · 2024Article
- Microtubule Cytoskeletal Network Alterations in a Transgenic Model of Tuberous Sclerosis Complex: Relevance to Autism Spectrum Disorders.International journal of molecular sciences · 2023Article
- A prognostic model based on necroptosis-related genes for prognosis and therapy in bladder cancer.BMC urology · 2023Article
- Investigating miR-9 as a mediator in laryngeal cancer health disparities.Frontiers in oncology · 2023Article
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- Review
- Susceptibility of cytoskeletal-associated proteins for tumor progression.Cellular and molecular life sciences : CMLS · 2021Review
- Article
- Deciphering the Role of Autophagy in Treatment of Resistance Mechanisms in Glioblastoma.International journal of molecular sciences · 2021Review
- Proteome and Phosphoproteome Analyses Reveal the Kinase Regulatory Network Involved in Glycogen Synthesis Kinase 3β.Frontiers in genetics · 2021Article
- Article
- Mitochondrial dysfunction contributes to Rapamycin-induced apoptosis of Human Glioblastoma Cells - A synergistic effect with Temozolomide.International journal of medical sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
Background: Clinical trials of therapies directed against nodes of the signaling axis of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin (mTOR) in glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin, and our analysis implicated a role for glycogen synthase kinase (GSK)3B attenuation in mediating resistance that was confirmed by functional studies. A targeted short hairpin RNA screen and further functional studies both in vitro and in vivo demonstrated that microtubule-associated protein (MAP)1B, previously associated predominantly with neurons, is a downstream effector of GSK3B-mediated resistance. Furthermore, we provide evidence that chronic rapamycin induces microtubule stability in a MAP1B-dependent manner in GBM cells. Additional experiments explicate a signaling pathway wherein combinatorial extracellular signal-regulated kinase (ERK)/mTOR targeting abrogates inhibitory phosphorylation of GSK3B, leads to phosphorylation of MAP1B, and confers sensitization. Conclusions: These data portray a compensatory molecular signaling network that imparts resistance to chronic mTOR inhibition in primary, human GBM cell cultures and points toward new therapeutic strategies.
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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.