精氨酸
生物
新陈代谢
下调和上调
精氨酸酶
重编程
氨基酸
生物化学
细胞生物学
基因
作者
Dirk Mossmann,Christoph Müller,Sujin Park,Brendan Ryback,Marco Colombi,Nathalie Ritter,Diana Weißenberger,Eva Dazert,Mairene Coto‐Llerena,Sandro Nuciforo,Lauriane Blukacz,Caner Ercan,Verónica Jiménez,Salvatore Piscuoglio,Fátima Bosch,Luigi Terracciano,Uwe Sauer,Markus H. Heim,Michael N. Hall
出处
期刊:Cell
[Elsevier]
日期:2023-11-01
卷期号:186 (23): 5068-5083.e23
被引量:24
标识
DOI:10.1016/j.cell.2023.09.011
摘要
Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in murine and patient hepatocellular carcinoma (HCC), despite reduced expression of arginine synthesis genes. Tumor cells accumulate high levels of arginine due to increased uptake and reduced arginine-to-polyamine conversion. Importantly, the high levels of arginine promote tumor formation via further metabolic reprogramming, including changes in glucose, amino acid, nucleotide, and fatty acid metabolism. Mechanistically, arginine binds RNA-binding motif protein 39 (RBM39) to control expression of metabolic genes. RBM39-mediated upregulation of asparagine synthesis leads to enhanced arginine uptake, creating a positive feedback loop to sustain high arginine levels and oncogenic metabolism. Thus, arginine is a second messenger-like molecule that reprograms metabolism to promote tumor growth.
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