ArticleBritish journal of cancer2020
ASCT2 (SLC1A5)-dependent glutamine uptake is involved in the progression of head and neck squamous cell carcinoma.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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93 citing papers in PubMed, 120 citations in OpenAlex.
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- Melatonin and Selected Phytochemicals: A Promising Combination to Target Altered Metabolism in Cancer.Nutrients · 2026Review
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- Role and clinical importance of lactylation in tumors (Review).Molecular medicine reports · 2026Review
- Overview of glutamine metabolism in stromal components of the tumor microenvironment and potential anti-tumor therapies.Genes & diseases · 2026Review
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- The role of L-type amino acid transporter 1 in the pathogenicity ofMicrobiology spectrum · 2026Article
- Metabolomic Insights into Head and Neck Cancer: Recent Advances and Future Directions.Current oncology (Toronto, Ont.) · 2026Review
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Blocking glutamine transport normalizes lymphatic vessels in hypoxic environments by attenuating glycolysis.bioRxiv : the preprint server for biology · 2026Article
- ALDH1L1 reverses CD8Journal of translational medicine · 2026Article
- Metabolic Messengers: Extracellular Vesicles as Central Mediators of Metabolic Reprogramming in Renal Cell Cancer.Biomedicines · 2026Review
- Mechanisms of mTORC1 and GCN2 amino acid sensing pathways in tumorigenesis and metastatic progression (Review).International journal of molecular medicine · 2026Review
- NEDD4 suppresses ferroptosis in lung ischemia-reperfusion injury by ubiquitinating and degrading SLC1A5.Scientific reports · 2025Article
- Article
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- Inhibition of integrin α3 suppresses gastric cancer progression via STAT3-mediated regulation of SLC1A5-dependent glutamine uptake.Journal of gastroenterology · 2025Article
- Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundGlutamine is an abundant and versatile nutrient in cancer cells. Head and neck squamous cell carcinoma (HNSCC) was reported to be dependent on mainly glucose, not glutamine, for producing the energy required for survival and proliferation.
methodsThe roles of ASCT2 (SLC1A5) and associated glutamine metabolism were determined by the MTT, colony formation, glutamine uptake, intracellular glutathione, ROS detection, immunofluorescence, immunohistochemistry, and apoptosis enzyme-linked immunosorbent assays as well as animal studies.
resultsWe found that glutamine is also critical for HNSCC. In this study, ASCT2, an amino acid transporter responsible for glutamine transport, in addition to LAT1 and GLS, is overexpressed in HNSCC and associated with poor survival. Using both in vivo and in vitro models, we found that knocking down ASCT2 by shRNAs or miR-137 or the combination of silencing ASCT2 and pharmacologically inhibiting SNAT2 via a small-molecule antagonist called V-9302 significantly suppressed intracellular glutamine levels and downstream glutamine metabolism, including glutathione production; these effects attenuated growth and proliferation, increased apoptosis and autophagy, and increased oxidative stress and mTORC1 pathway suppression in HNSCC. Additionally, silencing ASCT2 improved the response to cetuximab in HNSCC.
conclusionsIn summary, ASCT2-dependent glutamine uptake and subsequent glutamine metabolism are essential for HNSCC tumorigenesis, and the combination of glutamine uptake inhibitors and cetuximab presents a promising strategy for improving the outcomes of HNSCC patients.
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