[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-328718-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-328718-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","p53-orchestrates-cancer-metabolism-unveiling-strategies-to-reverse-the-warburg-effect","p53 Orchestrates Cancer Metabolism - Unveiling Strategies to Reverse the Warburg Effect","","Cancer cells reprogram metabolism by lowering oxidative phosphorylation (OXPHOS) while increasing glycolysis reliance, even under oxygen-replete conditions, a shift central to the Warburg effect. This metabolic rewiring supports uncontrolled growth, invasion, and therapeutic resistance, yet the molecular control logic remains unclear. The study presents a comprehensive mathematical model incorporating key p53 targets, showing p53 can drive metabolism toward an OXPHOS-dominant state with simulations matching colon cancer glucose metabolism comparisons. It further indicates high p53 activation can fully reverse the Warburg effect, including effects relevant to treatment resistance beyond apoptosis; for p53 mutations, it compares glycolysis-targeting versus SCO2-focused strategies.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/p53-orchestrates-cancer-metabolism-unveiling-strategies-to-reverse-the-warburg-effect/328718/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/p53-orchestrates-cancer-metabolism-unveiling-strategies-to-reverse-the-warburg-effect/328718.png","ImageObject",300,407,{"name":42,"@type":43},"Theodore","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-11","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What metabolic change defines the Warburg effect in cancer cells?","Question",{"text":63,"@type":64},"Cancer cells reduce oxidative phosphorylation (OXPHOS) and rely more on glycolysis, generating increased lactate even when oxygen is available.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does p53 influence cancer metabolism according to the study?",{"text":68,"@type":64},"The work proposes that p53 orchestrates its targets to redirect metabolism toward an OXPHOS-dominant state, with model simulations aligning with experimental data in colon cancer cells.",{"name":70,"@type":61,"acceptedAnswer":71},"What does the study suggest for therapy strategies when p53 is mutated?",{"text":72,"@type":64},"For p53 mutations, the analysis suggests targeting glycolysis-instigating signaling pathways as an alternative strategy; targeting SCO2 alone may not effectively suppress glycolysis.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},328718,1790788571,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,111,115,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":108,"show_sort_weight":109,"slug":110},7,"Healthcare",40,"healthcare",{"id":112,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":113,"slug":114},8,30,"research-report",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":112,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145,"preview_page_count":4},7971461740886,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Bulletin of Mathematical Biology (2024) 86:124  \n[https://doi.org/10.1007/s1](https://doi.org/10.1007/s1)1538-024-01346-5  \nORIGINAL ARTICLE  \np53 Orchestrates Cancer Metabolism: Unveiling Strategies to Reverse the Warburg Effect  \nRoba Abukwaik1,2 · Elias Vera-Siguenza2,3 · Daniel Tennant3 · Fabian Spill2  \nReceived: 26 April 2024 / Accepted: 30 July 2024 / Published online: 29 August 2024 © The Author(s) 2024  \nAbstract  \nCancer cells exhibit significant alterations in their metabolism, characterised by a reduction in oxidative phosphorylation (OXPHOS) and an increased reliance on glycolysis, even in the presence of oxygen. This metabolic shift, known as the Warburg effect, is pivotal in fuelling cancer’s uncontrolled growth, invasion, and therapeutic resistance. While dysregulation of many genes contributes to this metabolic shift, the tumour suppressor gene p53 emerges as a master player. Yet, the molecular mechanisms remain elusive. This study introduces a comprehensive mathematical model, integrating essential p53 targets, offering insights into how p53 orchestrates its targets to redirect cancer metabolism towards an OXPHOS-dominant state. Simulation outcomes align closely with experimental data comparing glucose metabolism in colon cancer cells with wild-type and mutated p53 . Additionally, our findings reveal the dynamic capability of elevated p53 activation to fully reverse the Warburg effect, highlighting the significance of its activity levels not just in triggering apoptosis (programmed cell death) post-chemotherapy but also in modifying the metabolic pathways implicated in treatment resistance. In scenarios of p53 mutations, our analysis suggests targeting glycolysis-instigating signalling pathways as an alternative strategy, whereas targeting solely synthesis of cytochrome c oxidase 2 (SCO2) does support mitochondrial respiration but may not effectively suppress the glycolysis pathway, potentially boosting the energy production and cancer cell viability.  \nB Roba Abukwaik[rabukwaik@kau.edu.sa](rabukwaik@kau.edu.sa)  \nB Fabian Spill [f.spill@bham.ac.uk](f.spill@bham.ac.uk)  \nElias Vera-Siguenza  \n[e.vera-siguenza@bham.ac.uk](e.vera-siguenza@bham.ac.uk)  \nDaniel Tennant  \n[d.tennant@bham.ac.uk](d.tennant@bham.ac.uk)  \n1 Mathematics Department, King Abdulaziz University, Rabigh, Saudi Arabia  \n2 School of Mathematics, University of Birmingham, Birmingham B15 2TS, UK  \n3 Institute of Metabolism and Systems Research, University of Birmingham, Birmingham B15 2TT, UK  \nKeywords Cancer metabolism · p53 · Warburg effect · Glycolysis · Hypoxia · Mathematical biology  \n1 Introduction  \nCancer cells undergo profound metabolic alterations facilitating their proliferation, invasion, metastasis, and even drug resistance (Han et al. 2013; Rahman and Hasan 2015) . Unlike normal cells, cancer cells derive a substantial amount of their energy from glycolysis, converting a majority of incoming glucose into lactate in the cytoplasm rather than metabolising it in the mitochondria through oxidative phosphorylation (OXPHOS) (Cairns et al. 2011; Simabuco et al. 2018) . This metabolic adaptation, recognised as the Warburg effect or aerobic glycolysis, leads to decreased oxygen consumption required by mitochondrial respiration while generating an increased amount of lactate (Simabuco et al. 2018) .  \nBy favouring glycolysis over OXPHOS, cancer cells ensure the availability of essential building blocks for biomass synthesis and meet the energy demands necessary for their rapid growth (Hanahan and Weinberg 2011; Simabuco et al. 2018). While glycolysis can produce adenosine triphosphate (ATP), the major cellular energy unit, more rapidly than oxidative phosphorylation, it is significantly less efficient in terms of ATP generated per unit of glucose consumed (Cairns et al. 2011; Simabuco et al. 2018) . Consequently, tumour cells increase their glucose uptake at an exceptionally high rate to adequately satisfy their elevated energy and biosynthesis","cbCaimBojUSzOf3A","https://ap.wps.com/l/cbCaimBojUSzOf3A","pdf",2255972,64,"English","# Introduction\n## Cancer metabolic reprogramming and the Warburg effect\n## Signaling pathways influencing glycolysis (PI3K/AKT/mTOR, HIF1)\n## Role of p53 in tumor suppression and metabolic regulation\n# Abstract","[{\"question\":\"What metabolic change defines the Warburg effect in cancer cells?\",\"answer\":\"Cancer cells reduce oxidative phosphorylation (OXPHOS) and rely more on glycolysis, generating increased lactate even when oxygen is available.\"},{\"question\":\"How does p53 influence cancer metabolism according to the study?\",\"answer\":\"The work proposes that p53 orchestrates its targets to redirect metabolism toward an OXPHOS-dominant state, with model simulations aligning with experimental data in colon cancer cells.\"},{\"question\":\"What does the study suggest for therapy strategies when p53 is mutated?\",\"answer\":\"For p53 mutations, the analysis suggests targeting glycolysis-instigating signaling pathways as an alternative strategy; targeting SCO2 alone may not effectively suppress glycolysis.\"}]","p53 Orchestrates Cancer Metabolism - Unveiling Strategies to Reverse the Warburg Effect | PDF",1789980708,161]