ArticleCellular and molecular neurobiology2019
Mammalian Target of Rapamycin 2 (MTOR2) and C-MYC Modulate Glucosamine-6-Phosphate Synthesis in Glioblastoma (GBM) Cells Through Glutamine: Fructose-6-Phosphate Aminotransferase 1 (GFAT1).
Article in Cellular and molecular neurobiology, 2019. 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 It has been retracted, and should not be counted.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 23 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
23 citing papers in PubMed, 35 citations in OpenAlex.
- mTOR in radiotherapy of lung cancer: Mechanisms of radiation resistance and therapeutic implications (Review).International journal of oncology · 2026Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth.Science advances · 2025Article
- Metabolism and signaling crosstalk in glioblastoma progression and therapy resistance.Molecular oncology · 2025Review
- Metformin and glioma: Targeting metabolic dysregulation for enhanced therapeutic outcomes.Translational oncology · 2025Review
- O-GlcNAcylation mediates Wnt-stimulated bone formation by rewiring aerobic glycolysis.EMBO reports · 2024Article
- Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals.The Journal of biological chemistry · 2024Review
- The "Superoncogene" Myc at the Crossroad between Metabolism and Gene Expression in Glioblastoma Multiforme.International journal of molecular sciences · 2023Review
- Role of glycolysis in inflammatory bowel disease and its associated colorectal cancer.Frontiers in endocrinology · 2023Review
- Improved antitumor activity against prostate cancer via synergistic targeting of Myc and GFAT-1.Theranostics · 2023Article
- PI3K/AKT/mTOR pathway, hypoxia, and glucose metabolism: Potential targets to overcome radioresistance in small cell lung cancer.Cancer pathogenesis and therapy · 2023Review
- A metabolic shift toward glycolysis enables cancer cells to maintain survival upon concomitant glutamine deprivation and V-ATPase inhibition.Frontiers in nutrition · 2023Article
- Nutrient-sensitive protein O-GlcNAcylation shapes daily biological rhythms.Open biology · 2022Review
- TGF-β links glycolysis and immunosuppression in glioblastoma.Histology and histopathology · 2021Review
- Role of glutamine and its metabolite ammonia in crosstalk of cancer-associated fibroblasts and cancer cells.Cancer cell international · 2021Review
- Metabolic Remodeling in Glioma Immune Microenvironment: Intercellular Interactions Distinct From Peripheral Tumors.Frontiers in cell and developmental biology · 2021Review
- Emerging Roles and Therapeutic Interventions of Aerobic Glycolysis in Glioma.OncoTargets and therapy · 2020Review
- GFAT1/HBP/O-GlcNAcylation Axis RegulatesBioMed research international · 2020Article
- Combination of Rapamycin and MK-2206 Induced Cell DeathFrontiers in pharmacology · 2020Article
Corrections and comments
- Correction · 2019-08-14Concerns/Issues about Authorship/Affiliation · Upgrade/Update of Prior Notice(s) · · Yi-Xiang See, Xin Chen, Zi-Kai Chen and Ze-Bin Huang removed as authors;
- Expression of concern · 2019-06-07Concerns/Issues about Authorship/Affiliation · Lack of Approval from Author · Updated to Correction ·
- Erratum issued
- Expression of concern
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Glucose and glutamine are two essential ingredients for cell growth. Glycolysis and glutaminolysis can be linked by glutamine: fructose-6-phosphate aminotransferase (GFAT, composed of GFAT1 and GFAT2) that catalyzes the synthesis of glucosamine-6-phosphate and glutamate by using fructose-6-phosphate and glutamine as substrates. The role of mammalian target of rapamycin (MTOR, composed of MTOR1 and MTOR2) in regulating glycolysis has been explored in human cancer cells. However, whether MTOR can interact with GFAT to regulate glucosamine-6-phosphate is poorly understood. In this study, we report that GFAT1 is essential to maintain the malignant features of GBM cells. And MTOR2 rather than MTOR1 plays a robust role in promoting GFAT1 protein activity, and accelerating the progression of glucosamine-6-phosphate synthesis, which is not controlled by the PI3K/AKT signaling. Intriguingly, high level of glucose or glutamine supply promotes MTOR2 protein activity. In turn, up-regulating glycolytic and glutaminolytic metabolisms block MTOR dimerization, enhancing the release of MTOR2 from the MTOR complex. As a transcriptional factor, C-MYC, directly targeted by MTOR2, promotes the relative mRNA expression level of GFAT1. Notably, our data reveal that GFAT1 immunoreactivity is positively correlated with the malignant grades of glioma patients. Kaplan-Meier assay reveals the correlations between patients' 5-year survival and high GFAT1 protein expression. Taken together, we propose that the MTOR2/C-MYC/GFAT1 axis is responsible for the modulation on the crosstalk between glycolysis and glutaminolysis in GBM cells. Under the condition of accelerated glycolytic and/or glutaminolytic metabolisms, the MTOR2/C-MYC/GFAT1 axis will be up-regulated in GBM cells.
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.