[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-343814-105":59,"doc-detail-343814-en":129},{"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":122,"head_meta":124,"extra_data":126,"updated_unix":128},105,"en","selective-metabolic-regulations-by-p53-mutant-variants-in-pancreatic-cancer","Selective metabolic regulations by p53 mutant variants in pancreatic cancer","","Mutations in the p53 tumor suppressor are present in roughly half of human cancers and can generate neomorphic p53 proteins with gain-of-function activity. Clinical relevance and variant-specific selectivity remain unresolved. The study compares mouse p53R270H and p53R172H variants using integrated global metabolomics plus epigenomic and transcriptomic profiling, and validates metabolic effects with oxygen consumption and functional assays in pancreatic cancer models, supported by human clinical dataset analyses.",{"@graph":69,"@context":121},[70,84,104],{"@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":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/selective-metabolic-regulations-by-p53-mutant-variants-in-pancreatic-cancer/343814/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/selective-metabolic-regulations-by-p53-mutant-variants-in-pancreatic-cancer/343814.png","ImageObject",300,407,{"name":92,"@type":93},"Quinn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What biological question does the study address about p53 mutations?","Question",{"text":111,"@type":112},"It evaluates how gain-of-function p53 mutant variants specifically regulate metabolism in pancreatic cancer and whether individual variants have distinct effects.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How were metabolic effects of p53R270H and p53R172H assessed?",{"text":116,"@type":112},"The work integrates global metabolomic analysis with epigenomic and transcriptomic profiling, measures oxygen consumption rate, and includes proliferation and cell–cell competition assays. Clinical dataset analyses further support the findings.",{"name":118,"@type":109,"acceptedAnswer":119},"What key metabolic differences were found between the two p53 mutant variants?",{"text":120,"@type":112},"p53R270H sustains mitochondrial function and energy production and influences antioxidant capacity, while p53R172H does not alter mitochondrial metabolism but attenuates pro-tumorigenic metabolic pathways such as the urea cycle.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},343814,1790052217,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":143},962075114765,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Caporali et al. J Exp Clin Cancer Res (2024) 43:310 [https://doi.org/10.1186/s13046-024-03232-3](https://doi.org/10.1186/s13046-024-03232-3)  \nJournal of Experimental & Clinical Cancer Research  \n RESEARCH Open Access  \nSelective metabolic regulations by p53 mutant variants in pancreatic cancer  \nSabrina Caporali1†, Alessio Butera1†, Alessia Ruzza 1†, Carlotta Zampieri2, Marina Bantula’3, Sandra Scharsich1, Anna‑Katerina Ückert4, Ivana Celardo4, Ian U. Kouzel5, Luigi Leanza6, Andreas Gruber5, Joan Montero3,7, Angelo D’Alessandro8, Thomas Brunner9, Marcel Leist4 and Ivano Amelio1*  \nAbstract  \nBackground Approximately half of all human cancers harbour mutations in the p53 gene, leading to the generation of neomorphic p53 mutant proteins. These mutants can exert gain‑of‑function (GOF) effects, potentially promoting tumour progression. However, the clinical significance of p53 GOF mutations, as well as the selectivity of individual variants, remains controversial and unclear.  \nMethods To elucidate the metabolic regulations and molecular underpinnings associated with the specific p53R270Hand p53R172H mutant variants (the mouse equivalents of human p53R273H and p53R175H, respectively), we employed a comprehensive approach. This included integrating global metabolomic analysis with epigenomic and transcrip‑ tomic profiling in mouse pancreatic cancer cells. Additionally, we assessed metabolic parameters such as oxygen consumption rate and conducted analyses of proliferation and cell–cell competition to validate the biological impact of metabolic changes on pancreatic ductal adenocarcinoma (PDAC) phenotype. Our findings were further corrobo‑ rated through analysis of clinical datasets from human cancer cohorts.  \nResults Our investigation revealed that the p53R270H variant, but not p53R172H, sustains mitochondrial function and energy production while also influencing cellular antioxidant capacity. Conversely, p53R172H, while not affect‑ ing mitochondrial metabolism, attenuates the activation of pro‑tumorigenic metabolic pathways such as the urea cycle. Thus, the two variants selectively control different metabolic pathways in pancreatic cancer cells. Mecha‑ nistically, p53R270H induces alterations in the expression of genes associated with oxidative stress and reduction in mitochondrial respiration. In contrast, p53R172H specifically impacts the expression levels of enzymes involved in the urea metabolism. However, our analysis of cell proliferation and cell competition suggested that the expression of either p53R270H or p53R172H does not influence confer any selective advantage to this cellular model in vitro. Fur‑ thermore, assessment of mitochondrial priming indicated that the p53R270H‑driven mitochondrial effect does not alter cytochrome c release or the apoptotic propensity of pancreatic cancer cells.  \nConclusions Our study elucidates the mutant‑specific impact of p53R270H and p53R172H on metabolism of PDAC cancer cells, highlighting the need to shift from viewing p53 mutant variants as a homogeneous group of entities to a systematic assessment of each specific p53 mutant protein. Moreover, our finding underscores the importance of further exploring the significance of p53 mutant proteins using models that more accurately reflect tumor ecology.  \n†Sabrina Caporali, Alessio Butera and Alessia Ruzza equally contributed to this article.  \n*Correspondence: Ivano Amelio  \nivano. amelio@uni‑[konstanz.de](konstanz.de)  \nFull list of author information is available at the end of the article  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included","cbCaihfG9FggNhOB","https://ap.wps.com/l/cbCaihfG9FggNhOB","pdf",6196352,17,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction","[{\"question\":\"What biological question does the study address about p53 mutations?\",\"answer\":\"It evaluates how gain-of-function p53 mutant variants specifically regulate metabolism in pancreatic cancer and whether individual variants have distinct effects.\"},{\"question\":\"How were metabolic effects of p53R270H and p53R172H assessed?\",\"answer\":\"The work integrates global metabolomic analysis with epigenomic and transcriptomic profiling, measures oxygen consumption rate, and includes proliferation and cell–cell competition assays. Clinical dataset analyses further support the findings.\"},{\"question\":\"What key metabolic differences were found between the two p53 mutant variants?\",\"answer\":\"p53R270H sustains mitochondrial function and energy production and influences antioxidant capacity, while p53R172H does not alter mitochondrial metabolism but attenuates pro-tumorigenic metabolic pathways such as the urea cycle.\"}]","Selective metabolic regulations by p53 mutant variants in pancreatic cancer | PDF",43]