Arginine reprograms metabolism in liver cancer via RBM39.
AGMAT
ARG1
ASNS
RBM39
arginine
hepatocellular carcinoma
indisulam
metabolism
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
09 11 2023
09 11 2023
Historique:
received:
09
12
2022
revised:
01
06
2023
accepted:
12
09
2023
medline:
13
11
2023
pubmed:
8
10
2023
entrez:
7
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37804830
pii: S0092-8674(23)01032-2
doi: 10.1016/j.cell.2023.09.011
pmc: PMC10642370
pii:
doi:
Substances chimiques
Arginine
94ZLA3W45F
HCC1 autoantigen
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5068-5083.e23Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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