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MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer.

Authors
  • Venkateswaran, Niranjan1
  • Conacci-Sorrell, Maralice1, 2, 3
  • 1 Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
  • 2 Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
  • 3 Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Type
Published Article
Journal
Cell Stress
Publisher
Shared Science Publishers OG
Publication Date
Jan 03, 2020
Volume
4
Issue
1
Pages
24–26
Identifiers
DOI: 10.15698/cst2020.01.210
PMID: 31922097
PMCID: PMC6946015
Source
PubMed Central
Keywords
License
Green

Abstract

Tryptophan is one of the eight essential amino acids that must be obtained from the diet. Interestingly, tryptophan is the least abundant amino acid in most proteins, a large portion of cellular tryptophan is converted into metabolites of the serotonin and kynurenine pathways. In a recent study, (Venkateswaran, Lafita-Navarro et al., 2019, Genes Dev), we discovered that colon cancer cells display greater uptake and processing of tryptophan than normal colonic cells and tissues. This process is mediated by the oncogenic transcription factor MYC that promotes the expression of the tryptophan importers SLC1A5 and SLC7A5 and the tryptophan metabolizing enzyme AFMID. The metabolism of tryptophan in colon cancer cells generates kynurenine, a biologically active metabolite necessary to maintain continuous cell proliferation. Our results indicate that kynurenine functions as an oncometabolite, at least in part, by activating the transcription factor AHR, which then regulates growth promoting genes in cancer cells. We propose that blocking kynurenine production or activity can be an efficient approach to specifically limit the growth of colon cancer cells. Here, we describe our findings and new questions for future studies targeted at understanding AHR-independent function of kynurenine, as well as interfering with the enzyme AFMID as a new strategy to target the kynurenine pathway.

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