ArticleThe Journal of biological chemistry2011
SLC6A14 (ATB0,+) protein, a highly concentrative and broad specific amino acid transporter, is a novel and effective drug target for treatment of estrogen receptor-positive breast cancer.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 202 citations in OpenAlex.
- Emerging roles of SLC6A14 in digestive system diseases: from amino acid transport to therapeutic targeting.Molecular biology reports · 2026Review
- Dual targeting of SLC6A14 and autophagy/macropinocytosis enhances therapeutic efficacy in pancreatic ductal adenocarcinoma.The Biochemical journal · 2026Article
- Selective Regimes and Evolutionary Dynamics of Z and W Gametologs Across an Expanded Avian Neo-Sex Chromosome.Genome biology and evolution · 2026Article
- Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.Journal of advanced research · 2026Review
- Lachnospiraceae-Derived Extracellular Vesicles Mediate the Cardioprotective Effects of Barley Leaf in Myocardial Infarction by Improving Intestinal Stem Cell Function.Journal of extracellular vesicles · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Unveiling the Structure of PROT and ATBMolecules (Basel, Switzerland) · 2025Article
- Landscape of metabolic alterations and treatment strategies in breast cancer.Genes & diseases · 2025Review
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Review
- Effects of lithium on mortality and metabolite profiles in Drosophila lithium-inducible SLC6 transporter mutants.Environmental toxicology and pharmacology · 2025Article
- The Kynurenine Pathway and Indole Pathway in Tryptophan Metabolism Influence Tumor Progression.Cancer medicine · 2025Review
- A hormetic response model for glutamine stress in cancer.Trends in cancer · 2025Review
- Article
- α-Methyl-Tryptophan Inhibits SLC6A14 Expression and Exhibits Immunomodulatory Effects in Crohn's Disease.Journal of inflammation research · 2025Article
- Transmembrane Amino Acid Transporters in Shaping the Metabolic Profile of Breast Cancer Cell Lines: The Focus on Molecular Biological Subtype.Current issues in molecular biology · 2024Review
- Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer.The EMBO journal · 2024Article
- Tumor energy metabolism: implications for therapeutic targets.Molecular biomedicine · 2024Review
- ASCT2 is a major contributor to serine uptake in cancer cells.Cell reports · 2024Article
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
55 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
SLC6A14, also known as ATB(0,+), is an amino acid transporter with unique characteristics. It transports 18 of the 20 proteinogenic amino acids. However, this transporter is expressed only at low levels in normal tissues. Here, we show that the transporter is up-regulated specifically in estrogen receptor (ER)-positive breast cancer, demonstrable with primary human breast cancer tissues and human breast cancer cell lines. SLC6A14 is an estrogen/ER target. The transport features of SLC6A14 include concentrative transport of leucine (an activator of mTOR), glutamine (an essential amino acid for nucleotide biosynthesis and substrate for glutaminolysis), and arginine (an essential amino acid for tumor cells), suggesting that ER-positive breast cancer cells up-regulate SLC6A14 to meet their increased demand for these amino acids. Consequently, treatment of ER-positive breast cancer cells in vitro with α-methyl-DL-tryptophan (α-MT), a selective blocker of SLC6A14, induces amino acid deprivation, inhibits mTOR, and activates autophagy. Prolongation of the treatment with α-MT causes apoptosis. Addition of an autophagy inhibitor (3-methyladenine) during α-MT treatment also induces apoptosis. These effects of α-MT are specific to ER-positive breast cancer cells, which express the transporter. The ability of α-MT to cause amino acid deprivation is significantly attenuated in MCF-7 cells, an ER-positive breast cancer cell line, when SLC6A14 is silenced with shRNA. In mouse xenograft studies, α-MT by itself is able to reduce the growth of the ER-positive ZR-75-1 breast cancer cells. These studies identify SLC6A14 as a novel and effective drug target for the treatment of ER-positive breast cancer.
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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.