Investigation of Roles of SLC38A1 in Proliferation and Differentiation of Mouse Tongue Epithelium and Expression in Human Oral Tongue Squamous Cell Carcinoma.
In: Cancers, Jg. 16 (2024-01-15), Heft 2, S. 405-419
Online
academicJournal
Zugriff:
Simple Summary: Alteration of metabolic pathways, including the activation of aerobic glycolysis and increased dependence on glutamine, is characteristic of several human cancer types. Slc38a1 (also known as SNAT1, SAT1, SA2 or ATA1) is a cell membrane transporter highly capable of the net accumulation of cellular glutamine. It has been shown to be upregulated in several human cancers and/or associated with tumor progression. However, the functional role of this protein in the proliferation and differentiation of the oral epithelium, and its expression in human oral tongue squamous cell carcinoma (OTSCC), is not well understood. This study shows the upregulated expression of SLC38A1 in OTSCC indicating a role of SLC38A1 in OTSCC progression. The aerobic glycolytic pathway, boosting lactate formation, and glutamine addiction are two hallmarks of cancer pathophysiology. Consistent with this, several cell membrane glutamine transporters, belonging to different solute carrier (SLC) families, have been shown to be upregulated in a cell-specific manner to furnish the cells with glutamine and glutamine-derived metabolic intermediates. Among them, the system A transporter Slc38a1 has a higher affinity for glutamine compared to other SLC transporters, and it undergoes highly multifaceted regulation at gene and protein levels. The current study aimed to investigate the functional role of Slc38a1 in the proliferation and maturation of the mouse tongue epithelium. Secondly, we aimed to examine the expression of SLC38A1 and its regulation in human tongue oral squamous cell carcinoma (OTSCC). Employing Slc38a1 wild-type and knockout mice, we showed that Slc38a1 was not directly linked to the regulation of the proliferation and differentiation of the mouse tongue epithelium. External transcriptomic datasets and Western blot analyses showed upregulation of SLC38A1 mRNA/protein in human OTSCC and oral cancer cell lines as compared to the corresponding controls. Further, an investigation of external datasets indicated that mechanisms other than the amplification of the SLC38A1 chromosomal locus or hypomethylation of the SLC38A1 promoter region might be important for the upregulation of SLC38A1 in OTSCC. [ABSTRACT FROM AUTHOR]
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Investigation of Roles of SLC38A1 in Proliferation and Differentiation of Mouse Tongue Epithelium and Expression in Human Oral Tongue Squamous Cell Carcinoma.
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Autor/in / Beteiligte Person: | Sapkota, Dipak ; Wang, Daxin ; Schreurs, Olaf ; Vallenari, Evan M. ; Pandey Dhakal, Sushma ; Küntziger, Thomas ; Toközlü, Burcu Sengüven ; Utheim, Tor Paaske ; Chaudhry, Farrukh Abbas |
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Zeitschrift: | Cancers, Jg. 16 (2024-01-15), Heft 2, S. 405-419 |
Veröffentlichung: | 2024 |
Medientyp: | academicJournal |
ISSN: | 2072-6694 (print) |
DOI: | 10.3390/cancers16020405 |
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