2. Academic Validation
  3. SNAT1 (SLC38A1) Is Not the Main Glutamine Transporter in Melanoma, but Controls Metabolism via Glutamine-Dependent Activation of P62 (SQSTM1)/cMYC-Axis

SNAT1 (SLC38A1) Is Not the Main Glutamine Transporter in Melanoma, but Controls Metabolism via Glutamine-Dependent Activation of P62 (SQSTM1)/cMYC-Axis

  • Cancers (Basel). 2026 Mar 25;18(7):1068. doi: 10.3390/cancers18071068.
Sandra Lörentz 1,  Ines Böhme-Schäfer 1 2,  Jörg König 3 4,  Heinrich Sticht 5,  Anja Katrin Bosserhoff 1 6 7 8
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Medicine, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Fahrstraße 17, 91054 Erlangen, Germany.
  • 2 Department Hamm 2, Hochschule Hamm Lippstadt, Marker Allee 76-78, 59063 Hamm, Germany.
  • 3 Department of Clinical Pharmacology and Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Fahrstraße 17, 91054 Erlangen, Germany.
  • 4 FAU NeW Research Center New Bioactive Compounds, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, Germany.
  • 5 Division of Bioinformatics, Institute of Biochemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Fahrstraße 17, 91054 Erlangen, Germany.
  • 6 Bavarian Cancer Research Center (BZKF), 91054 Erlangen, Germany.
  • 7 CCC Erlangen-EMN: Comprehensive Cancer Center Erlangen-EMN, 91054 Erlangen, Germany.
  • 8 CCC WERA: Comprehensive Cancer Center Alliance WERA, 91054 Erlangen, Germany.
PMID: 41976291 DOI: 10.3390/cancers18071068
Abstract

Background: Tumor cells can reprogram their metabolism, constituting a hallmark of Cancer that plays a crucial role in tumor progression. As tumor cells exhibit an increased demand for nutrients, e.g., Amino acids, they rely on extracellular sources and show deregulation of transport proteins. Among these, SNAT1 (SLC38A1) is described as the loader for glutamine that is responsible for the main influx of this amino acid. The aim of this study was to assess the molecular function of SNAT1 in melanoma regarding its role in amino acid transport and regulation of cellular metabolism. Methods: siPool-mediated downregulation of SNAT1 expression in melanoma cell lines was used to investigate the molecular function of this protein. Glutamine transport was assessed by measuring the intracellular and extracellular concentrations of glutamine. Regulation of downstream effectors was evaluated with qRT-PCR and Western Blot. Metabolism was investigated by performing Seahorse flux analysis. Mitochondrial staining was examined via flow cytometry. Protein interaction was assessed with Co-IP, and in silico modeling of protein interaction was performed with AlphaFold3. Results: In this study, we uncovered the new finding that SNAT1 is not primarily implicated in glutamine influx into melanoma cells but in signaling in response to extracellular glutamine. We identified p62 and cMYC as downstream effectors of SNAT1. By activating the p62/cMYC-axis and target genes of cMYC, SNAT1 modulates the metabolism of melanoma cells depending on the glutamine level. SNAT1 and p62 are interaction partners. Conclusions: This finding newly suggests that SNAT1 may function as a sensor or receptor ("transceptor") for glutamine rather than being a direct and primary glutamine transporter, and could open up new therapeutic options targeting melanoma cells.

Keywords

SNAT1 (SLC38A1); glutamine transport; melanoma; transceptor; tumor metabolism.

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