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Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Authors :
Venkateswaran, Niranjan
Garcia, Roy
Lafita-Navarro, M. Carmen
Yi-Heng Hao
Perez-Castro, Lizbeth
Nogueira, Pedro A. S.
Solmonson, Ashley
Mender, Ilgen
Kilgore, Jessica A.
Shun Fang
Brown, Isabella N.
Li Li
Parks, Emily
dos Santos, Igor Lopes
Bhaskar, Mahima
Kim, Jiwoong
Yuemeng Jia
Lemoff, Andrew
Grishin, Nick V.
Kinch, Lisa
Source :
Nature Communications; 5/20/2024, Vol. 15 Issue 1, p1-17, 17p, 1 Diagram, 8 Graphs
Publication Year :
2024

Abstract

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20411723
Volume :
15
Issue :
1
Database :
Complementary Index
Journal :
Nature Communications
Publication Type :
Academic Journal
Accession number :
178341026
Full Text :
https://doi.org/10.1038/s41467-024-47868-3