2019
DOI: 10.1101/gad.327056.119
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MYC promotes tryptophan uptake and metabolism by the kynurenine pathway in colon cancer

Abstract: Tumors display increased uptake and processing of nutrients to fulfill the demands of rapidly proliferating cancer cells. Seminal studies have shown that the proto-oncogene MYC promotes metabolic reprogramming by altering glutamine uptake and metabolism in cancer cells. How MYC regulates the metabolism of other amino acids in cancer is not fully understood. Using high-performance liquid chromatography (HPLC)-tandem mass spectrometry (LC-MS/MS), we found that MYC increased intracellular levels of tryptophan and… Show more

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Cited by 150 publications
(176 citation statements)
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“…In colonic cells, MYC promotes the expression of the tryptophan transporters (SLC7A5 and SLC1A5) and enzyme arylformamidase in the kynurenine pathway, thereby driving the conversion of tryptophan into kynurenine. 34 Of note, high levels of kynurenine can increase the proliferation and migratory capacity of cancer cells, and help tumors escape immune surveillance. 35 In addition to MYC, HIF-2α, the Hippo pathway effectors, the hormone receptors, and the stress response factor ATF4 were shown to upregulate SLC7A5 and/or SLC43A1 expression in multiple cancer types, including clear cell renal carcinoma, hepatocellular carcinoma, breast and prostate cancers, [36][37][38][39][40] which leads to elevated EAA uptake and aggressive tumor progression.…”
Section: Myc Regulation Of Glucose Metabolismmentioning
confidence: 99%
“…In colonic cells, MYC promotes the expression of the tryptophan transporters (SLC7A5 and SLC1A5) and enzyme arylformamidase in the kynurenine pathway, thereby driving the conversion of tryptophan into kynurenine. 34 Of note, high levels of kynurenine can increase the proliferation and migratory capacity of cancer cells, and help tumors escape immune surveillance. 35 In addition to MYC, HIF-2α, the Hippo pathway effectors, the hormone receptors, and the stress response factor ATF4 were shown to upregulate SLC7A5 and/or SLC43A1 expression in multiple cancer types, including clear cell renal carcinoma, hepatocellular carcinoma, breast and prostate cancers, [36][37][38][39][40] which leads to elevated EAA uptake and aggressive tumor progression.…”
Section: Myc Regulation Of Glucose Metabolismmentioning
confidence: 99%
“…Finally, we note the presence in this cluster of dodecanedioic acid metabolite. The accumulation of this metabolite is associated with an impairment of fatty acid oxidation at the carnitine palmitoyl transferase (CPT) level 28 , an effect in line with the observed overall reduction of acylcarnitine pools.…”
Section: Biological Effects Of Exposure To Dphp Through Metabolomics mentioning
confidence: 57%
“…Finally, we noticed that the lowest DPhP concentration reduced the expression of genes related to the tryptophan and the xenobiotic metabolism ( Figure 6D). This was intriguing since tryptophan metabolites have been connected to aryl metabolism and the xenobiotic receptor AHR 28,29 . To improve sample clustering, we then tested by OPLS-DA all possible combinations able to discriminate our 4 groups of replicates, using the control replicates as negative controls.…”
Section: Biological Effects Of Dphp Exposure Through Transcriptomic Amentioning
confidence: 99%
“…While it has been shown convincingly that SLC1A5, SLC7A5, SLC7A11, and SLC6A14 are all up-regulated in specific cancer types, molecular mechanisms underlying this up-regulation remain to be explored in greater detail. With regard to SLC1A5 and SLC7A5, the oncogene MYC appears to be at least one of the drivers of up-regulation [44,45]. In the present study, we investigated the molecular mechanism associated with the up-regulation of SLC6A14 in colon cancer.…”
Section: Discussionmentioning
confidence: 95%