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

Author

Listed:
  • 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
    University of Texas Southwestern Medical Center)

  • Lisa Kinch

    (University of Texas Southwestern Medical Center
    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
    University of Texas Southwestern Medical Center)

  • Ralph J. DeBerardinis

    (Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Hao Zhu

    (Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Maralice Conacci-Sorrell

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

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.

Suggested Citation

  • 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, 2024. "Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47868-3
    DOI: 10.1038/s41467-024-47868-3
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    References listed on IDEAS

    as
    1. Evan C. Lien & Anna M. Westermark & Yin Zhang & Chen Yuan & Zhaoqi Li & Allison N. Lau & Kiera M. Sapp & Brian M. Wolpin & Matthew G. Vander Heiden, 2021. "Low glycaemic diets alter lipid metabolism to influence tumour growth," Nature, Nature, vol. 599(7884), pages 302-307, November.
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