Arginine reprograms metabolism in liver cancer via 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…

• NS
  National Science Foundation
• AV
  Alexander von Humboldt-Stiftung
• S
  Sjöbergstiftelsen
• DF
  Deutsche Forschungsgemeinschaft
• LF
  Louis-Jeantet Foundation
• SN
  Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
• CD
  Centro de Investigación e Innovación en Energía Marina
• ER
  European Research Council
• HE
  H2020 European Research Council
• NC
  NCCR Catalysis