Kynurenine: an oncometabolite in colon cancer.

IF 4.1 Q2 CELL BIOLOGY Cell Stress Pub Date : 2020-01-03 DOI:10.15698/cst2020.01.210
Niranjan Venkateswaran, Maralice Conacci-Sorrell
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引用次数: 38

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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犬尿氨酸:结肠癌中的一种肿瘤代谢物。
色氨酸是必须从饮食中获得的八种必需氨基酸之一。有趣的是,色氨酸是大多数蛋白质中含量最少的氨基酸,细胞色氨酸的很大一部分被转化为血清素和犬尿氨酸途径的代谢物。在最近的一项研究中(Venkateswaran, lafata - navarro等人,2019,Genes Dev),我们发现结肠癌细胞比正常的结肠细胞和组织对色氨酸的吸收和处理更多。这一过程是由致癌转录因子MYC介导的,MYC促进色氨酸进口蛋白SLC1A5和SLC7A5以及色氨酸代谢酶AFMID的表达。结肠癌细胞中色氨酸的代谢产生犬尿氨酸,一种维持细胞连续增殖所必需的生物活性代谢物。我们的研究结果表明,犬尿氨酸作为一种肿瘤代谢物,至少在一定程度上是通过激活转录因子AHR发挥作用的,AHR随后调节癌细胞中促进生长的基因。我们提出,阻断犬尿氨酸的产生或活性可能是一种有效的方法,可以特异性地限制结肠癌细胞的生长。在这里,我们描述了我们的发现和未来研究的新问题,旨在了解犬尿氨酸不依赖ahr的功能,以及干扰AFMID酶作为靶向犬尿氨酸途径的新策略。
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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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