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European Archives of Oto-Rhino-Laryngology

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01.02.2016 | Head and Neck

Glutaminolysis and carcinogenesis of oral squamous cell carcinoma

verfasst von: Marcel Cetindis, Thorsten Biegner, Adelheid Munz, Peter Teriete, Siegmar Reinert, Martin Grimm

Erschienen in: European Archives of Oto-Rhino-Laryngology | Ausgabe 2/2016

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Abstract

Glutaminolysis is a crucial factor for tumor metabolism in the carcinogenesis of several tumors but has not been clarified for oral squamous cell carcinoma (OSCC) yet. Expression of glutaminolysis-related solute carrier family 1, member 5 (SLC1A5)/neutral amino acid transporter (ASCT2), glutaminase (GLS), and glutamate dehydrogenase (GLDH) was analyzed in normal oral mucosa (n = 5), oral precursor lesions (simple hyperplasia, n = 11; squamous intraepithelial neoplasia, SIN I–III, n = 35), and OSCC specimen (n = 42) by immunohistochemistry. SLC1A5/ASCT2 and GLS were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue, while GLDH was weakly detected. Compared with SIN I–III SLC1A5/ASCT2 and GLS expression were significantly increased in OSCC. GLDH expression did not significantly differ from SIN I–III compared with OSCC. This study shows the first evidence of glutaminolysis-related SLC1A5/ASCT2, GLS, and GLDH expression in OSCC. The very weak GLDH expression indicates that glutamine metabolism is rather related to nucleotide or protein/hexosamine biosynthesis or to the function as an antioxidant (glutathione) than to energy production or generation of lactate through entering the tricarboxylic acid cycle. Overcoming glutaminolysis by targeting c-Myc oncogene (e.g. by natural compounds) and thereby cross-activation of mammalian target of rapamycin complex 1 or SLC1A5/ASCT2, GLS inhibitors may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.

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Titel: Glutaminolysis and carcinogenesis of oral squamous cell carcinoma
verfasst von: Marcel Cetindis
Thorsten Biegner
Adelheid Munz
Peter Teriete
Siegmar Reinert
Martin Grimm
Publikationsdatum: 01.02.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: European Archives of Oto-Rhino-Laryngology / Ausgabe 2/2016
Print ISSN: 0937-4477
Elektronische ISSN: 1434-4726
DOI: https://doi.org/10.1007/s00405-015-3543-7

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Glutaminolysis and carcinogenesis of oral squamous cell carcinoma

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