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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 | Maralice Conacci-Sorrell
Nature communications | 2024

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.

Pubmed ID: 38769298

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA245548
  • Agency: NCI NIH HHS, United States
    Id: R35 CA220449
  • Agency: Division of Cancer Prevention, National Cancer Institute (NCI Division of Cancer Prevention),
    Id: NCI R01CA245548
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM145744
  • Agency: NCI NIH HHS, United States
    Id: R01 CA251928
  • Agency: NCI NIH HHS, United States
    Id: P30 CA142543

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This is a list of tools and resources that we have found mentioned in this publication.


SAMTOOLS (tool)

RRID:SCR_002105

Original SAMTOOLS package has been split into three separate repositories including Samtools, BCFtools and HTSlib. Samtools for manipulating next generation sequencing data used for reading, writing, editing, indexing,viewing nucleotide alignments in SAM,BAM,CRAM format. BCFtools used for reading, writing BCF2,VCF, gVCF files and calling, filtering, summarising SNP and short indel sequence variants. HTSlib used for reading, writing high throughput sequencing data.

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STAR (tool)

RRID:SCR_004463

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Bowtie (tool)

RRID:SCR_005476

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HTSeq (tool)

RRID:SCR_005514

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on February 28,2023. Software Python package that provides infrastructure to process data from high-throughput sequencing assays. While the main purpose of HTSeq is to allow you to write your own analysis scripts, customized to your needs, there are also a couple of stand-alone scripts for common tasks that can be used without any Python knowledge.

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Bioconductor (tool)

RRID:SCR_006442

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RRID:SCR_011847

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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NCBI Assembly Archive Viewer (tool)

RRID:SCR_012917

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Abcam (tool)

RRID:SCR_012931

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Proteome Discoverer (tool)

RRID:SCR_014477

Software for identifying, characterizing, and quantifying proteins in biological samples. Can be used for range of proteomics workflows such as protein and peptide identification, PTM analysis, and isobaric mass tagging for quantification. Supports multiple database search algorithms and multiple dissociation techniques.

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DESeq2 (tool)

RRID:SCR_015687

Software package for differential gene expression analysis based on the negative binomial distribution. Used for analyzing RNA-seq data for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates.

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