Kynurenine: an oncometabolite in colon cancer
Authors:Niranjan Venkateswaran1 and Maralice Conacci-Sorrell1,2,3
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.
Keywords:
tryptophan, kynurenine, IDO1, TDO2, colon cancer, MYC, AHR.
Corresponding Author(s):
Conflict of interest statement:
Authors report no conflict of interest.
Please cite this article as:
Niranjan Venkateswaran and Maralice Conacci-Sorrell (2020). Kynurenine: an oncometabolite in colon cancer. Cell Stress 4(1): 24-26. doi: 10.15698/cst2020.01.210
© 2020 Venkateswaran and Conacci-Sorrell. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and repro-duction in any medium, provided the original author and source are acknowledged.
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.