TY - JOUR
T1 - Kynurenine
T2 - An oncometabolite in colon cancer
AU - Venkateswaran, Niranjan
AU - Conacci-Sorrell, Maralice
N1 - Funding Information:
We are grateful to the Sorrell lab members and Dr. Katherine Luby-Phelps for their valuable input. This research was supported by Cancer Prevention and Research Institute of Texas RR150059, American Cancer Society IRG-17-174-13, Welch I-1914, and University of Texas Southwestern Circle of Friends Early Investigator Award to M.C-S. M.C-S is the Virginia Murchison Linthicum Scholar in Medical Research.
PY - 2020/1
Y1 - 2020/1
N2 - 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.
AB - 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.
KW - AHR
KW - Colon cancer
KW - IDO1
KW - Kynurenine
KW - MYC
KW - TDO2
KW - Tryptophan
UR - http://www.scopus.com/inward/record.url?scp=85090347223&partnerID=8YFLogxK
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U2 - 10.15698/cst2020.01.210
DO - 10.15698/cst2020.01.210
M3 - Review article
C2 - 31922097
AN - SCOPUS:85090347223
VL - 4
SP - 24
EP - 26
JO - Cell Stress
JF - Cell Stress
SN - 2523-0204
IS - 1
ER -