Arginine reprograms metabolism in liver cancer via RBM39
Menée à l'aide de lignées cellulaires, d'organoïdes ainsi que d'échantillons tumoraux et d'échantillons tissulaires sains prélevés sur des patients atteints d'un carcinome hépatocellulaire, cette étude met en évidence un mécanisme par lequel l'arginine modifie le métabolisme hépatique via la protéine RBM39
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.
Cell , article en libre accès, 2022