The SLC38A5 /SNAT5 amino acid transporter: from pathophysiology to pro-cancer roles in the tumor microenvironment.

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  • Additional Information
    • Source:
      Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901225 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1522-1563 (Electronic) Linking ISSN: 03636143 NLM ISO Abbreviation: Am J Physiol Cell Physiol Subsets: MEDLINE
    • Publication Information:
      Original Publication: Bethesda, Md. : American Physiological Society,
    • Subject Terms:
      Amino Acid Transport Systems, Neutral*/genetics ; Amino Acid Transport Systems, Neutral*/metabolism ; Neoplasms*/genetics; Pregnancy ; Female ; Humans ; Glutamine ; Asparagine ; Tumor Microenvironment ; Amino Acid Transport Systems ; Amino Acids ; Serine
    • Abstract:
      SLC38A5 /SNAT5 is a system N transporter that can mediate net inward or outward transmembrane fluxes of neutral amino acids coupled with Na + (symport) and H + (antiport). Its preferential substrates are not only amino acids with side chains containing amide (glutamine and asparagine) or imidazole (histidine) groups, but also serine, glycine, and alanine are transported by the carrier. Expressed in the pancreas, intestinal tract, brain, liver, bone marrow, and placenta, it is regulated at mRNA and protein levels by mTORC1 and WNT/β-catenin pathways, and it is sensitive to pH, nutritional stress, inflammation, and hypoxia. SNAT5 expression has been found to be altered in pathological conditions such as chronic inflammatory diseases, gestational complications, chronic metabolic acidosis, and malnutrition. Growing experimental evidence shows that SNAT5 is overexpressed in several types of cancer cells. Moreover, recently published results indicate that SNAT5 expression in stromal cells can support the metabolic exchanges occurring in the tumor microenvironment of asparagine-auxotroph tumors. We review the functional role of the SNAT5 transporter in pathophysiology and propose that, due to its peculiar operational and regulatory features, SNAT5 may play important pro-cancer roles when expressed either in neoplastic or in stromal cells of glutamine-auxotroph tumors. NEW & NOTEWORTHY The transporter SLC38A5 /SNAT5 provides net influx or efflux of glutamine, asparagine, and serine. These amino acids are of particular metabolic relevance in several conditions. Changes in transporter expression or activity have been described in selected types of human cancers, where SNAT5 can mediate amino acid exchanges between tumor and stromal cells, thus providing a potential therapeutic target. This is the first review that recapitulates the characteristics and roles of the transporter in physiology and pathology.
    • Contributed Indexing:
      Keywords: amino acid transport; asparagine; cancer; glutamine; metabolic diseases
    • Accession Number:
      0RH81L854J (Glutamine)
      0 (Amino Acid Transport Systems, Neutral)
      7006-34-0 (Asparagine)
      0 (Amino Acid Transport Systems)
      0 (Amino Acids)
      452VLY9402 (Serine)
      0 (SLC38A5 protein, human)
    • Publication Date:
      Date Created: 20230717 Date Completed: 20230809 Latest Revision: 20230815
    • Publication Date:
      20240829
    • Accession Number:
      10.1152/ajpcell.00169.2023
    • Accession Number:
      37458433