ArticleThe EMBO journal2019
SLC1A3 contributes to L-asparaginase resistance in solid tumors.
Article in The EMBO journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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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.
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Who cites it
46 citing papers in PubMed, 72 citations in OpenAlex.
- Synergistic apoptotic induction in acute lymphoblastic leukemia cells: exploring the role of EAAT1 inhibition by UCPH-101 in combination with asparaginase.Molecular biology reports · 2026Article
- Bridging the Gap in Lung Cancer: Novel Biomarkers, Metabolic Drivers, and Advanced Therapeutics from Bench to Bedside.Biomedicines · 2026Article
- Solute Carrier transporters in tumor metabolism and immune modulation: implications for therapy.Journal of translational medicine · 2026Review
- Tumor metabolic adaptation induced by L-asparaginase reveals a vulnerability to PARP1/2 inhibitor in B-cell lymphomas.Nature communications · 2026Article
- Surface Avidity of Anionic Polypeptide Coatings on Layer-by-Layer Nanoparticles Target Cancer-Associated Amino Acid Transporters.Angewandte Chemie (International ed. in English) · 2026Article
- Article
- Autophagy-targeted intervention synergized with pegaspargase: an innovative therapeutic paradigm for pancreatic cancer.Cancer cell international · 2025Article
- Repurposing Asparaginase Therapy to Target Cisplatin-Resistant Cancer Cells.Fundamental & clinical pharmacology · 2025Article
- Genetic variations in amino acid metabolism-related genes are associated with risk of papillary thyroid carcinoma: a case-control study.BMC endocrine disorders · 2025Article
- Prognostic signature and tumor microenvironment infiltration based on amino acid metabolism-related genes and lncRNAs of colorectal cancer.Scientific reports · 2025Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Receptor-Mediated Internalization of L-Asparaginase into Tumor Cells Is Suppressed by Polyamines.International journal of molecular sciences · 2025Article
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- A Recent Overview of Molecular Pathways in Synthetic Lethality as a Proposed Valid Target in Oncology: Current Insights and Future Directions.Indian journal of surgical oncology · 2025Review
- Marine-derived L-asparaginase: unlocking marine power in anti-tumor therapeutics.Frontiers in immunology · 2025Review
- Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.International journal of cancer · 2025Article
- Loss of Carbamoyl Phosphate Synthetase 1 Potentiates Hepatocellular Carcinoma Metastasis by Reducing Aspartate Level.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The glutamate/aspartate transporter EAAT1 is crucial for T-cell acute lymphoblastic leukemia proliferation and survival.Haematologica · 2024Article
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Emerging roles of small extracellular vesicles in metabolic reprogramming and drug resistance in cancers.Cancer drug resistance (Alhambra, Calif.) · 2024Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
L-asparaginase (ASNase) serves as an effective drug for adolescent acute lymphoblastic leukemia. However, many clinical trials indicated severe ASNase toxicity in patients with solid tumors, with resistant mechanisms not well understood. Here, we took a functional genetic approach and identified SLC1A3 as a novel contributor to ASNase resistance in cancer cells. In combination with ASNase, SLC1A3 inhibition caused cell cycle arrest or apoptosis, and myriads of metabolic vulnerabilities in tricarboxylic acid (TCA) cycle, urea cycle, nucleotides biosynthesis, energy production, redox homeostasis, and lipid biosynthesis. SLC1A3 is an aspartate and glutamate transporter, mainly expressed in brain tissues, but high expression levels were also observed in some tumor types. Here, we demonstrate that ASNase stimulates aspartate and glutamate consumptions, and their refilling through SLC1A3 promotes cancer cell proliferation. Lastly, in vivo experiments indicated that SLC1A3 expression promoted tumor development and metastasis while negating the suppressive effects of ASNase by fueling aspartate, glutamate, and glutamine metabolisms despite of asparagine shortage. Altogether, our findings identify a novel role for SLC1A3 in ASNase resistance and suggest that restrictive aspartate and glutamate uptake might improve ASNase efficacy with solid tumors.
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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.