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

Niranjan Venkateswaran, Roy Garcia, M. Carmen Lafita-Navarro, Yi-Heng Hao, Lizbeth Perez-Castro, Pedro A. S. Nogueira, Ashley Solmonson, Ilgen Mender, Jessica A. Kilgore, Shun Fang, Isabella N. Brown, Li Li, Emily Parks, Igor Lopes dos Santos, Mahima Bhaskar, Jiwoong Kim, Yuemeng Jia, Andrew Lemoff, Nick V. Grishin, Lisa Kinch, Lin Xu, Noelle S. Williams, Jerry W. Shay, Ralph J. DeBerardinis, Hao Zhu and Maralice Conacci-Sorrell ()
Additional contact information
Niranjan Venkateswaran: University of Texas Southwestern Medical Center
Roy Garcia: University of Texas Southwestern Medical Center
M. Carmen Lafita-Navarro: University of Texas Southwestern Medical Center
Yi-Heng Hao: University of Texas Southwestern Medical Center
Lizbeth Perez-Castro: University of Texas Southwestern Medical Center
Pedro A. S. Nogueira: University of Texas Southwestern Medical Center
Ashley Solmonson: Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
Ilgen Mender: University of Texas Southwestern Medical Center
Jessica A. Kilgore: University of Texas Southwestern Medical Center
Shun Fang: University of Texas Southwestern Medical Center
Isabella N. Brown: University of Texas Southwestern Medical Center
Li Li: University of Texas Southwestern Medical Center
Emily Parks: University of Texas Southwestern Medical Center
Igor Lopes dos Santos: University of Texas Southwestern Medical Center
Mahima Bhaskar: University of Texas Southwestern Medical Center
Jiwoong Kim: University of Texas Southwestern Medical Center
Yuemeng Jia: Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
Andrew Lemoff: University of Texas Southwestern Medical Center
Nick V. Grishin: University of Texas Southwestern Medical Center
Lisa Kinch: University of Texas Southwestern Medical Center
Lin Xu: University of Texas Southwestern Medical Center
Noelle S. Williams: University of Texas Southwestern Medical Center
Jerry W. Shay: University of Texas Southwestern Medical Center
Ralph J. DeBerardinis: Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
Hao Zhu: Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
Maralice Conacci-Sorrell: University of Texas Southwestern Medical Center

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47868-3 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47868-3

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47868-3

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().