Arginine reprograms metabolism in liver cancer via RBM39
Mossmann, Dirk (Biozentrum, University of Basel)
Müller, Christoph (Biozentrum, University of Basel)
Park, Sujin (Biozentrum, University of Basel)
Ryback, Brendan (Institute of Molecular Systems Biology)
Colombi, Marco (Biozentrum, University of Basel)
Ritter, Nathalie (Biozentrum, University of Basel)
Weißenberger, Diana (Biozentrum, University of Basel)
Dazert, Eva (Biozentrum, University of Basel)
Coto Llerena, Mairene (University of Basel. Department of Biomedicine)
Nuciforo, Sandro (University of Basel)
Blukacz, Lauriane (University of Basel)
Ercan, Caner (University of Basel)
Jimenez, Veronica (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Piscuoglio, Salvatore (University of Basel)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Terracciano, Luigi M. (University of Basel)
Sauer, Uwe (Institute of Molecular Systems Biology)
Heim, Markus H. (University of Basel)
Hall, Michael N. (Biozentrum, University of Basel)

Fecha:	2023
Descripción:	40 pàg.
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Cell, Vol. 186, Núm. 23 (november 2023) , p. 5068-5083.e23, ISSN 1097-4172

DOI: 10.1016/j.cell.2023.09.011
PMID: 37804830

40 p, 11.1 MB

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