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Arginine reprograms metabolism in liver cancer via RBM39.

ABSTRACT: 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.

SUBMITTER: Mossmann D

PROVIDER: S-EPMC10642370 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Arginine reprograms metabolism in liver cancer via RBM39.

Mossmann Dirk D Müller Christoph C Park Sujin S Ryback Brendan B Colombi Marco M Ritter Nathalie N Weißenberger Diana D Dazert Eva E Coto-Llerena Mairene M Nuciforo Sandro S Blukacz Lauriane L Ercan Caner C Jimenez Veronica V Piscuoglio Salvatore S Bosch Fatima F Terracciano Luigi M LM Sauer Uwe U Heim Markus H MH Hall Michael N MN

Cell 20231006 23

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 argin ...[more]

PMID: 37804830

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Arginine reprograms metabolism in liver cancer via RBM39.

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Arginine reprograms metabolism in liver cancer via RBM39.

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