ArticleCarcinogenesis2021
Inhibition of GFAT1 in lung cancer cells destabilizes PD-L1 protein.
Article in Carcinogenesis, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Efficacy of LNP@2DG-DON liposomal nanoparticles in tumor inhibition and immune activation.Journal of translational medicine · 2026Article
- Decoding the Hexosamine Biosynthesis Pathway: Implications for Novel Therapeutic Strategies in Sarcoma.Journal of cellular physiology · 2026Review
- Review
- Dysfunctional decidual CD2Frontiers in immunology · 2026Article
- O-GlcNAcylation at the tumor-immune interface: a metabolic post-translational code driving immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
- Glutamine: fructose-6-phosphate amidotransferase (GFAT) in the pathology of diseases: a review.Cell death discovery · 2025Review
- GFAT1 promotes the progression of hepatocellular carcinoma via enhancing the O-GlcNAcylation of VEZF1.Cell death & disease · 2025Article
- Exploring the metabolic signaling network of GFPT in cancer.Cell death discovery · 2025Review
- RNA‑binding protein MBNL1 regulates tumor growth, chemosensitivity and antitumor immunity in lung adenocarcinoma by controlling the expression of tumor suppressor RNF125.Oncology reports · 2025Article
- Multi-omics dissection of MAPK-driven senescence unveils therapeutic vulnerabilities in KIAA1549::BRAF-fusion pediatric low-grade glioma models.Signal transduction and targeted therapy · 2025Article
- GFPT1 accelerates immune escape in breast cancer by modifying PD-L1 via O-glycosylation.BMC cancer · 2024Article
- N-linked glycosylation of PD-L1/PD-1: an emerging target for cancer diagnosis and treatment.Journal of translational medicine · 2024Review
- Emerging therapeutic frontiers in cancer: insights into posttranslational modifications of PD-1/PD-L1 and regulatory pathways.Experimental hematology & oncology · 2024Review
- 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
- Current knowledge and potential intervention of hexosamine biosynthesis pathway in lung cancer.World journal of surgical oncology · 2023Review
- Review
- Regulation of post-translational modification of PD-L1 and advances in tumor immunotherapy.Frontiers in immunology · 2023Review
- Differential effects of glucose and N-acetylglucosamine on genome instability.American journal of cancer research · 2022Article
- Therapeutic Potential of Glutamine Pathway in Lung Cancer.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Immunotherapy using checkpoint blockers (antibodies) has been a major advance in recent years in the management of various types of solid cancers including lung cancer. One target of checkpoint blockers is programmed death ligand 1 (PD-L1) expressed by cancer cells, which engages programmed death 1 on T cells and Natural Killer (NK) cells resulting in suppression of their activation and cancer-killing function, respectively. Apart from antibodies, other clinically relevant agents that can inhibit PD-L1 are limited. PD-L1 protein stability depends on its glycosylation. Here we show that l-glutamine:d-fructose-6-phosphate amidotransferase 1 (GFAT1), a rate-limiting enzyme of the hexosamine biosynthesis pathway, which produces uridine diphosphate-N-acetyl-β-glucosamine, a precursor for glycosylation, is required for the stability of PD-L1 protein. Inhibition of GFAT1 activity markedly reduced interferon gamma (IFNγ)-induced PD-L1 levels in various lung cancer cell lines. GFAT1 inhibition suppressed glycosylation of PD-L1 and accelerated its proteasomal degradation. Importantly, inhibition of GFAT1 in IFNγ-treated cancer cells enhanced the activation of T cells and the cancer-killing activity of NK cells. These findings support using GFAT1 inhibitors to manipulate PD-L1 protein level that could augment the efficacy of immunotherapy for lung cancer.
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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.