Elevated arginine levels in liver tumors promote metabolic reprogramming and tumor growth

Mossmann, Dirk and Park, Sujin and Ryback, Brendan and Weißenberger, Diana and Colombi, Marco and Hindupur, Sravanth K. and Dazert, Eva and Coto-Llerena, Mairene and Caner, Ercan and Cenzano, Veronica J. and Piscuoglio, Salvatore and Bosch, Fatima and Terracciano, Luigi M. and Sauer, Uwe and Hall, Michael N.. (2022) Elevated arginine levels in liver tumors promote metabolic reprogramming and tumor growth.

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Official URL: https://edoc.unibas.ch/89781/

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Arginine auxotropy, due to reduced expression of urea cycle genes, is common in cancer. However, little is known about the levels of arginine in these cancers. Here, we report that arginine levels are elevated in hepatocellular carcinoma (HCC) despite reduced expression of urea cycle enzymes. Liver tumors accumulate high levels specifically of arginine via increased uptake and, more importantly, via suppression of arginine-to-polyamine conversion due to reduced arginase 1 (ARG1) and agmatinase (AGMAT) expression. Furthermore, the high levels of arginine are required for tumor growth. Mechanistically, high levels of arginine promote tumorigenesis via transcriptional regulation of metabolic genes, including upregulation of asparagine synthetase (ASNS). ASNS-derived asparagine further enhances arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a novel second messenger-like molecule that reprograms metabolism to promote tumor growth.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Growth & Development > Biochemistry (Hall)
UniBasel Contributors:Hall, Michael N.
Item Type:Preprint
Number of Pages:1-30
Note:Publication type according to Uni Basel Research Database: Discussion paper / Internet publication
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Last Modified:07 Sep 2022 14:19
Deposited On:07 Sep 2022 14:19

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