ArticleThe Journal of clinical investigation2014
Increased sugar uptake promotes oncogenesis via EPAC/RAP1 and O-GlcNAc pathways.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 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
119 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Does cancer risk increase with HbA1c, independent of diabetes?British journal of cancer · 2014Pooled it
- Semaglutide Alleviates LPS-Induced Cognitive Disorder via O-GlcNAcylation of AKT-mTOR Signaling Pathway Components.Neuromolecular medicine · 2026Article
- TIMP1 Derived from Mesenchymal Stem Cells Promotes Bladder Cancer Progression by Regulating the Formation of VDIMs through the RAP1 Pathway.International journal of biological sciences · 2026Article
- Leaflet-specific phospholipid imaging using genetically encoded proximity sensors.Nature chemical biology · 2026Article
- Cell cycle regulation in cancer cells by O-GlcNAcylation.Glycoconjugate journal · 2025Review
- Dietary Glycemic Index, Glycemic Load, and Risk of Lung Cancer: A Population-Based Cohort Study.Annals of family medicine · 2025Article
- Metabolomics as a tool for understanding and treating triple-negative breast cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Characterizing the tumor immune environment in thymic epithelial tumors using T-cell receptor repertoire analysis and gene expression profiling.JTCVS open · 2025Article
- The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma.Breast cancer research : BCR · 2024Article
- Biochemical hallmarks-targeting antineoplastic nanotherapeutics.Bioactive materials · 2024Review
- Nanotechnology and Cancer Bioelectricity: Bridging the Gap Between Biology and Translational Medicine.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma.Channels (Austin, Tex.) · 2023Article
- Rap1 in the Context of PCSK9, Atherosclerosis, and Diabetes.Current atherosclerosis reports · 2023Review
- SOX9 promotes the invasion and migration of lung adenocarcinoma cells by activating the RAP1 signaling pathway.BMC pulmonary medicine · 2023Article
- Targeting metabolism by B-raf inhibitors and diclofenac restrains the viability of BRAF-mutated thyroid carcinomas with Hif-1α-mediated glycolytic phenotype.British journal of cancer · 2023Article
- Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.International journal of molecular sciences · 2023Review
- Review
- Targeting integrin pathways: mechanisms and advances in therapy.Signal transduction and targeted therapy · 2023Review
- Functions and modulation of PKM2 activity by human papillomavirus E7 oncoprotein (Review).Oncology letters · 2023Review
- Molecular characteristics, clinical significance, and immune landscape of extracellular matrix remodeling-associated genes in colorectal cancer.Frontiers in oncology · 2023Article
59 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
3 authors at 2 institutions in 2 countries.
Funding
Abstract
There is a considerable resurgence of interest in the role of aerobic glycolysis in cancer; however, increased glycolysis is frequently viewed as a consequence of oncogenic events that drive malignant cell growth and survival. Here we provide evidence that increased glycolytic activation itself can be an oncogenic event in a physiologically relevant 3D culture model. Overexpression of glucose transporter type 3 (GLUT3) in nonmalignant human breast cells activated known oncogenic signaling pathways, including EGFR, β1 integrin, MEK, and AKT, leading to loss of tissue polarity and increased growth. Conversely, reduction of glucose uptake in malignant cells promoted the formation of organized and growth-arrested structures with basal polarity, and suppressed oncogenic pathways. Unexpectedly and importantly, we found that unlike reported literature, in 3D the differences between "normal" and malignant phenotypes could not be explained by HIF-1α/2α, AMPK, or mTOR pathways. Loss of epithelial integrity involved activation of RAP1 via exchange protein directly activated by cAMP (EPAC), involving also O-linked N-acetylglucosamine modification downstream of the hexosamine biosynthetic pathway. The former, in turn, was mediated by pyruvate kinase M2 (PKM2) interaction with soluble adenylyl cyclase. Our findings show that increased glucose uptake activates known oncogenic pathways to induce malignant phenotype, and provide possible targets for diagnosis and therapeutics.
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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.