ArticleThe Journal of clinical investigation2018
O-GlcNAcylation is required for mutant KRAS-induced lung tumorigenesis.
Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 81 citations in OpenAlex.
- Twist1 overexpression models an aggressive subtype of pancreatic ductal adenocarcinoma in vivo.Lab animal · 2026Article
- Decoding the regulatory code: O-GlcNAcylation in epithelial-mesenchymal transition (EMT).The Journal of biological chemistry · 2026Review
- A risk score model based on glycosylation-related genes for predicting radioresistance and prognosis of lung adenocarcinoma.Translational cancer research · 2026Article
- Regulatory mechanism of O-linked N-acetylglucosamine protein modification on autophagy in cancer.Clinical and translational medicine · 2026Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- Down-regulation of MFNG promotes the metastatic potential of lung adenocarcinoma by regulating TGF-β/Smad signaling.iScience · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- Sugar symphony: glycosylation in cancer metabolism and stemness.Trends in cell biology · 2025Review
- High-frequency KRAS mutations in pancreatic adenocarcinoma: prognostic significance and potential co-targeting therapies.Translational cancer research · 2025Article
- Post-translational modifications of protein and lung cancer.Frontiers in oncology · 2025Review
- Mir-615-3p promotes osteosarcoma progression via the SESN2/AMPK/mTOR pathway.Cancer cell international · 2024Article
- Prediction of prognosis, efficacy of lung adenocarcinoma by machine learning model based on immune and metabolic related genes.Discover oncology · 2024Article
- Altered glycosylation in cancer: molecular functions and therapeutic potential.Cancer communications (London, England) · 2024Review
- O-GlcNAcylation inhibition redirects the response of colon cancer cells to chemotherapy from senescence to apoptosis.Cell death & disease · 2024Article
- GFPT2 expression is induced by gemcitabine administration and enhances invasion by activating the hexosamine biosynthetic pathway in pancreatic cancer.Clinical & experimental metastasis · 2024Article
- Mass spectrometry analysis of intact proteinJournal of Zhejiang University. Science. B · 2024Article
- Nutlin-3a induces KRAS mutant/p53 wild type lung cancer specific methuosis-like cell death that is dependent on GFPT2.Journal of experimental & clinical cancer research : CR · 2023Article
- circ-hnRNPU inhibits NONO-mediated c-Myc transactivation and mRNA stabilization essential for glycosylation and cancer progression.Journal of experimental & clinical cancer research : CR · 2023Article
- Current knowledge and potential intervention of hexosamine biosynthesis pathway in lung cancer.World journal of surgical oncology · 2023Review
- Differential Detection of O-GlcNAcylated proteins in the heart using antibodies.Analytical biochemistry · 2023Article
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Authors and funding
23 authors at 3 institutions in 1 country.
Funding
Abstract
Mutant KRAS drives glycolytic flux in lung cancer, potentially impacting aberrant protein glycosylation. Recent evidence suggests aberrant KRAS drives flux of glucose into the hexosamine biosynthetic pathway (HBP). HBP is required for various glycosylation processes, such as protein N- or O-glycosylation and glycolipid synthesis. However, its function during tumorigenesis is poorly understood. One contributor and proposed target of KRAS-driven cancers is a developmentally conserved epithelial plasticity program called epithelial-mesenchymal transition (EMT). Here we showed in novel autochthonous mouse models that EMT accelerated KrasG12D lung tumorigenesis by upregulating expression of key enzymes of the HBP pathway. We demonstrated that HBP was required for suppressing KrasG12D-induced senescence, and targeting HBP significantly delayed KrasG12D lung tumorigenesis. To explore the mechanism, we investigated protein glycosylation downstream of HBP and found elevated levels of O-linked β-N-acetylglucosamine (O-GlcNAcylation) posttranslational modification on intracellular proteins. O-GlcNAcylation suppressed KrasG12D oncogene-induced senescence (OIS) and accelerated lung tumorigenesis. Conversely, loss of O-GlcNAcylation delayed lung tumorigenesis. O-GlcNAcylation of proteins SNAI1 and c-MYC correlated with the EMT-HBP axis and accelerated lung tumorigenesis. Our results demonstrated that O-GlcNAcylation was sufficient and required to accelerate KrasG12D lung tumorigenesis in vivo, which was reinforced by epithelial plasticity programs.
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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.