ArticleJournal of experimental & clinical cancer research : CR2018
LAT2 regulates glutamine-dependent mTOR activation to promote glycolysis and chemoresistance in pancreatic cancer.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 140 citations in OpenAlex.
- mRNA Network: Solution for Tracking Chemotherapy Insensitivity in Small-Cell Lung Cancer.Journal of healthcare engineering · 2021Trial
- Positive feedback loop via HIF-1α lactylation driven by kynurenine promotes glycolysis.Oncogene · 2026Article
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Metabolic plasticity in pancreatic ductal adenocarcinoma progression and response to treatment.Molecular cancer · 2026Review
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- The role of abnormal amino acid metabolism in the occurrence and development of tumors.Frontiers in oncology · 2026Review
- TGM2-P2RX7 loop promotes gemcitabine resistance in pancreatic cancer by modulating glutamine metabolism and mitophagy.Cell death discovery · 2025Article
- SLC6A14-mediated glutamine promotes SYTL4-CXCL8 axis activation to drive gemcitabine resistance and immune evasion in pancreatic cancer.Experimental & molecular medicine · 2025Article
- Inhibition Profiling ofMolecules (Basel, Switzerland) · 2025Article
- Glutamine: a new strategy for targeted metabolic therapy in the tumor microenvironment.Cell death discovery · 2025Review
- Beyond the tumor: Enhancing pancreatic cancer therapy through glutamine metabolism and innovative drug delivery.Journal of cell communication and signaling · 2025Review
- Ablation of LAT2 Transporter Causes Intramuscular Glutamine Accumulation and Inhibition of Fasting-Induced Proteolysis.Journal of cachexia, sarcopenia and muscle · 2025Article
- Targeting LAT1 with JPH203 to reduce TNBC proliferation and reshape suppressive immune microenvironment by blocking essential amino acid uptake.Amino acids · 2025Article
- Thyroid hormones inhibit tumor progression and enhance the antitumor activity of lenvatinib in hepatocellular carcinoma via reprogramming glucose metabolism.Cell death discovery · 2025Article
- Combination therapy of low-dose radiotherapy and immunotherapy in advanced metastatic nasopharyngeal carcinoma: a case report and literature review.Discover oncology · 2025Article
- Assessing the Causal Effect of Circulating Protein-To-Protein Ratio on the Risk of Morbidity of Hepatocellular Carcinoma.Cancer medicine · 2025Article
- cNEK6 induces gemcitabine resistance by promoting glycolysis in pancreatic ductal adenocarcinoma via the SNRPA/PPA2c/mTORC1 axis.Cell death & disease · 2024Article
- Emerging mechanisms and promising approaches in pancreatic cancer metabolism.Cell death & disease · 2024Review
- Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway.Scientific reports · 2024Article
- Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundReprogrammed energy metabolism has become an emerging hallmark of cancer in recent years. Transporters have been reported to be amino acid sensors involved in controlling mTOR recruitment and activation, which is crucial for the growth of both normal and tumor cells. L-type amino acid transporter 2 (LAT2), encoded by the SLC7A8 gene, is a Na
methodsThe effects of LAT2 on biological behaviors were analyzed. LAT2 and LDHB levels in tissues were detected, and the clinical value was evaluated.
resultsWe demonstrated that LAT2 emerged as an oncogenic protein and could decrease the gemcitabine sensitivity of pancreatic cancer cells in vitro and in vivo. The results of a survival analysis indicated that high expression levels of both LAT2 and LDHB predicted a poor prognosis in patients with pancreatic cancer. Furthermore, we found that LAT2 could promote proliferation, inhibit apoptosis, activate glycolysis and alter glutamine metabolism to activate mTOR in vitro and in vivo. Next, we found that gemcitabine combined with an mTOR inhibitor (RAD001) could reverse the decrease in chemosensitivity caused by LAT2 overexpression in pancreatic cancer cells. Mechanistically, we demonstrated that LAT2 could regulate two glutamine-dependent positive feedback loops (the LAT2/p-mTOR
conclusionTaken together, our data reveal that LAT2 functions as an oncogenic protein and could regulate glutamine-dependent mTOR activation to promote glycolysis and decrease GEM sensitivity in pancreatic cancer. The LAT2-mTOR-LDHB pathway might be a promising therapeutic target in pancreatic cancer.
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