ArticleThe Biochemical journal2021
Expression and function of SLC38A5, an amino acid-coupled Na+/H+ exchanger, in triple-negative breast cancer and its relevance to macropinocytosis.
Article in The Biochemical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Immunological and pathological characteristics of brain parenchymal and leptomeningeal metastases from non-small cell lung cancer.Cell discovery · 2025Article
- Soybean Cyst Nematode-Resistant Protein AATPlant direct · 2025Article
- Amino acid metabolism in breast cancer: pathogenic drivers and therapeutic opportunities.Protein & cell · 2025Review
- Loss of cadherin 17 downregulates LGR5 expression, stem cell properties and drug resistance in metastatic colorectal cancer cells.Cell death & disease · 2025Article
- Macropinocytosis mediates resistance to loss of glutamine transport in triple-negative breast cancer.The EMBO journal · 2024Article
- SLC38A5 suppresses ferroptosis through glutamine-mediated activation of the PI3K/AKT/mTOR signaling in osteosarcoma.Journal of translational medicine · 2024Article
- Article
- Oxidative Stress in Breast Cancer: A Biochemical Map of Reactive Oxygen Species Production.Current issues in molecular biology · 2024Review
- A glutamine tug-of-war between cancer and immune cells: recent advances in unraveling the ongoing battle.Journal of experimental & clinical cancer research : CR · 2024Review
- Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11.Antioxidants (Basel, Switzerland) · 2024Article
- Review
- Entry of nanoparticles into cells and tissues: status and challenges.Beilstein journal of nanotechnology · 2024Article
- SLC38A5 promotes glutamine metabolism and inhibits cisplatin chemosensitivity in breast cancer.Breast cancer (Tokyo, Japan) · 2024Article
- Glutamine addiction and therapeutic strategies in pancreatic cancer.World journal of gastrointestinal oncology · 2023Review
- Article
- Amino acid transporter SLC38A5 is a tumor promoter and a novel therapeutic target for pancreatic cancer.Scientific reports · 2023Article
- Impact of the polymer backbone chemistry on interactions of amino-acid-derived zwitterionic polymers with cells.Bioactive materials · 2023Article
- Article
- Expression and Function of StAR in Cancerous and Non-Cancerous Human and Mouse Breast Tissues: New Insights into Diagnosis and Treatment of Hormone-Sensitive Breast Cancer.International journal of molecular sciences · 2023Article
- Amplified CaInternational journal of cancer · 2022Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Metabolic reprogramming in cancer necessitates increased amino acid uptake, which is accomplished by up-regulation of specific amino acid transporters. However, not all tumors rely on any single amino acid transporter for this purpose. Here, we report on the differential up-regulation of the amino acid transporter SLC38A5 in triple-negative breast cancer (TNBC). The up-regulation is evident in TNBC tumors, conventional and patient-derived xenograft TNBC cell lines, and a mouse model of spontaneous TNBC mammary tumor. The up-regulation is confirmed by functional assays. SLC38A5 is an amino acid-dependent Na+/H+ exchanger which transports Na+ and amino acids into cells coupled with H+ efflux. Since cell-surface Na+/H+ exchanger is an established inducer of macropinocytosis, an endocytic process for cellular uptake of bulk fluid and its components, we examined the impact of SLC38A5 on macropinocytosis in TNBC cells. We found that the transport function of SLC38A5 is coupled to the induction of macropinocytosis. Surprisingly, the transport function of SLC38A5 is inhibited by amilorides, the well-known inhibitors of Na+/H+ exchanger. Down-regulation of SLC38A5 in TNBC cells attenuates serine-induced macropinocytosis and reduces cell proliferation significantly as assessed by multiple methods, but does not induce cell death. The Cancer Genome Atlas database corroborates SLC38A5 up-regulation in TNBC. This represents the first report on the selective expression of SLC38A5 in TNBC and its role as an inducer of macropinocytosis, thus revealing a novel, hitherto unsuspected, function for an amino acid transporter that goes beyond amino acid delivery but is still relevant to cancer cell nutrition and proliferation.
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