[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-341219-105":59,"doc-detail-341219-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","tryptophan-fuels-myc-dependent-liver-tumorigenesis-through-indole-3-pyruvate-synthesis","Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis","","MYC-driven liver tumors depend on enhanced tryptophan (Trp) uptake but show reduced utilization of Trp through the kynurenine (Kyn) pathway to produce metabolites. A no-Trp diet blocks the growth of MYC-dependent tumors and restores the transcriptional program of normal liver cells while leaving protein synthesis largely unaffected. The Trp-derived metabolite indole 3-pyruvate (I3P) is identified as a key driver of tumor growth. Supplementing I3P rescues tumor cell growth under Trp starvation, supporting I3P as a potential therapeutic target for MYC-driven cancers.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/tryptophan-fuels-myc-dependent-liver-tumorigenesis-through-indole-3-pyruvate-synthesis/341219/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/tryptophan-fuels-myc-dependent-liver-tumorigenesis-through-indole-3-pyruvate-synthesis/341219.png","ImageObject",300,407,{"name":92,"@type":93},"Ivy","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What metabolic dependency do MYC-driven liver tumors show regarding tryptophan?","Question",{"text":112,"@type":113},"MYC-driven liver tumors rely on augmented tryptophan uptake but have reduced tryptophan utilization through the kynurenine (Kyn) pathway to generate metabolites.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does a no-Trp diet affect MYC-dependent liver tumors and normal liver cells?",{"text":117,"@type":113},"Depriving MYC-driven tumors of Trp prevents tumor growth and restores the transcriptional profile of normal liver cells.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is indole 3-pyruvate (I3P) considered important for liver tumor growth?",{"text":121,"@type":113},"I3P, a Trp-derived metabolite, is shown to be crucial for liver tumor growth, and I3P supplementation restores growth even when cells are starved of Trp.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},341219,1790176928,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":139,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},549758252649,"https://ap-avatar.wpscdn.com/avatar/8000253669c5317157?_k=1778319167496531819","Article [https://doi.org/10.1038/s41467-024-47868-3](https://doi.org/10.1038/s41467-024-47868-3)  \nTryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis  \nReceived: 23 August 2022  \n\n| Accepted: 9 April 2024 |\n| --- |\n| |\n| Check for updates |\n\nNiranjan Venkateswaran1,9, Roy Garcia1,9, M. Carmen Lafita-Navarro1,9, Yi-Heng Hao1,9, Lizbeth Perez-Castro1,9, Pedro A. S. Nogueira1,9, Ashley Solmonson2, Ilgen Mender1, Jessica A. Kilgore3, Shun Fang1, Isabella N. Brown1, Li Li1, Emily Parks 1, Igor Lopes dos Santos 1, Mahima Bhaskar1, Jiwoong Kim 4, Yuemeng Jia2, Andrew Lemoff 3,  \nNick V. Grishin5,6, Lisa Kinch5,6, Lin Xu 4, NoelleS. Williams3, Jerry W. Shay 1,7, Ralph J. DeBerardinis 2,6,7, Hao Zhu 2,7,8 & Maralice Conacci-Sorrell 1,7,8   \nCancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors ofTrp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.  \nThrough the activity of oncogenes, cancer cells develop an increased ability to obtain nutrients and efficiently utilize them for biomass production and cell growth1. Recent studies explored the efficacy of limiting single dietary components in cancer treatment2–4. For example, methionine deprivation reduces the growth of colon cancer cells5–7, and asparagine deprivation prevents the growth of cancer cells  \nby altering mitochondrial function3. Furthermore, diets restricted inserine and glycine reduce cancer cell growth through the accumulation of deoxysphingolipids2–4. Because the different types of cancer vary in their metabolic activity, preferred energy source, and nutritional dependencies, characterization of nutrient demands by individual tumor types has the potential to identify their specific  \n1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 2Children’s Medical Center Research Institute at University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 3Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 4Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA. 5Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 6Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 7Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 8Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. 9These authors contributed equally: Niranjan Venkateswaran, Roy Garcia, M. Carmen Lafita-Navarro, Yi-Heng Hao, Lizbeth  \nPerez-Castro, Pedro A. S. Nogueira. [e-mail:](e-mail: Maralice.ConacciSorrell@UTSouthwestern.edu)[ Maralice.ConacciSorrell@UTSouthwestern.edu](e-mail: Maralice.ConacciSorrell@UTSouthwestern.edu)  \nvulnerabilities that can be safely manipulated through dietary orpharmacologic interventions to tar","cbCaiuePW1VGjnnS","https://ap.wps.com/l/cbCaiuePW1VGjnnS","pdf",4584957,17,"English","# Abstract\n## MYC-driven tryptophan dependency\n## Indole 3-pyruvate (I3P) role and therapeutic potential\n## Background: cancer metabolism and Trp/Kyn pathway","[{\"question\":\"What metabolic dependency do MYC-driven liver tumors show regarding tryptophan?\",\"answer\":\"MYC-driven liver tumors rely on augmented tryptophan uptake but have reduced tryptophan utilization through the kynurenine (Kyn) pathway to generate metabolites.\"},{\"question\":\"How does a no-Trp diet affect MYC-dependent liver tumors and normal liver cells?\",\"answer\":\"Depriving MYC-driven tumors of Trp prevents tumor growth and restores the transcriptional profile of normal liver cells.\"},{\"question\":\"Why is indole 3-pyruvate (I3P) considered important for liver tumor growth?\",\"answer\":\"I3P, a Trp-derived metabolite, is shown to be crucial for liver tumor growth, and I3P supplementation restores growth even when cells are starved of Trp.\"}]","Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis | PDF",1790040989,43]