[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-450368-105":59,"doc-detail-450368-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","mutant-p53-regulates-reversible-subtype-plasticity-in-pancreatic-cancer","Mutant p53 regulates reversible subtype plasticity in pancreatic cancer","","Loss-of-function mutations in TP53 are common in human malignancies, yet the oncogenic gain-of-function effects of missense variants remain unclear. Using genetically defined pancreatic cancer organoid models, the study shows mutant p53 confers a selective growth advantage during acute environmental stress and induces a transition to a basal-like gene expression program. Transcriptomic evidence links this stress-driven state to a poor-prognosis subtype, and the molecular subtype reverses when growth conditions normalize, indicating transcriptional plasticity driven by tissue microenvironment changes. Targeting mutant p53 is proposed as a therapeutic strategy.",{"@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":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/mutant-p53-regulates-reversible-subtype-plasticity-in-pancreatic-cancer/450368/",{"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/mutant-p53-regulates-reversible-subtype-plasticity-in-pancreatic-cancer/450368.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-07","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":19},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What did the study demonstrate about mutant p53 under acute stress?","Question",{"text":112,"@type":113},"Mutant p53 provided a selective growth advantage during acute environmental stress and drove a molecular transition toward a basal-like state in genetically defined pancreatic cancer organoid models.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How do transcriptomic analyses connect mutant p53 to pancreatic cancer subtype behavior?",{"text":117,"@type":113},"Under stress, organoids expressing mutant p53 adopted a basal-like gene expression program associated with poor prognosis, and the molecular subtype reverted to the classical subtype after conditions returned to normal.",{"name":119,"@type":110,"acceptedAnswer":120},"Why is mutant p53 suggested as a therapeutic target for pancreatic cancer?",{"text":121,"@type":113},"Because mutant p53 exhibits context-dependent oncogenic properties that influence growth and subtype plasticity in pancreatic cancer, targeting it may offer a promising therapeutic strategy.","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},450368,1791019892,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":19,"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":41},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Cellular and Molecular Life Sciences (2026) 83:31  \n[https://doi.org/10.1007/s00018-025-05945-w](https://doi.org/10.1007/s00018-025-05945-w) Cellular and Molecular Life Sciences  \nORIGINAL ARTICLE  \nMutant p53 regulates reversible subtype plasticity in pancreatic cancer  \nJune-Ha Shin1 · Hwa-Ryeon Kim1 · Jae-Seok Roe1  \nReceived: 23 May 2025 / Revised: 15 August 2025 / Accepted: 5 October 2025 © The Author(s) 2025, modified publication 2026  \nAbstract  \nLoss-of-function mutations in the TP53 gene are the most frequent genetic events in human malignancies. However, the extent to which missense TP53 mutations confer oncogenic gain-of-function (GOF) properties remains incompletely understood. Using genetically defined pancreatic cancer organoid models, we demonstrated that mutant p53 provides a selective growth advantage under acute environmental stress and drives molecular transition toward a basal-like state. Transcriptomic analyses showed that under stress conditions, organoids expressing mutant p53 adopted a basal-like gene expression program, a characteristic of a poor prognosis subtype of pancreatic cancer. Furthermore, the molecular subtype was reversed to the classical subtype once it returned to normal growth conditions, suggesting that transcriptional plasticity arises from acute changes in the tissue microenvironment. Given these context-dependent oncogenic properties, our findings suggest that targeting mutant p53 may be a promising therapeutic strategy for pancreatic cancer.  \nKeywords Pancreatic cancer · Mutant p53 · Gain-of-function · Subtype · Organoid  \nIntroduction  \nMutations in the TP53 gene rank among the most common genetic alterations in human cancers. Because approximately 80% of these variants are missense mutations in the DNA-binding domain [1], these mutations abolish the sequence-specific transcriptional activity of p53 and disrupt its ability to control cell cycle arrest, DNA repair, and apoptosis [2, 3] . Mutant p53 also exhibits oncogenic gainof-function (GOF) activity and supports tumor maintenance and progression [4, 5] . Mutant p53 has been suggested to co-opt various regulatory proteins and signaling pathways, thereby promoting cancer cell survival, invasion, and therapeutic resistance.  \nPrevious studies have identified multiple mechanisms through which mutant p53 directly contributes to carcinogenesis. In acute myeloid leukemia, mutant p53 co-optsthe pluripotency factor FOXH1 to activate aberrant stem  \n􀀍 Jae-Seok Roe [jroe@yonsei.ac.kr](jroe@yonsei.ac.kr)  \n1 Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul  \n03722, Republic of Korea  \ncell-like transcriptional programs, thereby enhancing the self-renewal of leukemic cell [6] . Additionally, deletion of mutant p53 (p53R172H) in triple-negative breast tumors induces substantial tumor regression via activation of the cGAS–STING pathway, highlighting its essential role in breast cancer maintenance [7] . Consistent with its oncogenic functions, mutant p53 has been implicated in the mediation of drug-resistant phenotypes. For instance, in ovarian cancer, mutant p53 promotes cell survival following paclitaxel treatment via the miR-130b–ZEB1 axis [8] . Furthermore, mutant p53 interacts directly with the ETS2 transcription factor, thereby impairing the cellular responses to DNA damage [9] . Collectively, these examples highlight the ability of mutant p53 to reprogram critical oncogenic  \npathways beyond its canonical tumor-suppressive role.  \nPancreatic ductal adenocarcinoma (PDAC) is driven by near-universal KRAS activation and frequent TP53 mutations (approximately 70% of cases) [10] . Although the loss of classical tumor-suppressive function explains how PDAC is initiated, the extent to which TP53 missense mutations actively contribute to additional malignancypromoting effects remains elusive. To date, Weissmueller et al. demonstrated that mouse models harboring hot-spot Trp53 missense mutations devel","cbCaiiNmZQvAWcqi","https://ap.wps.com/l/cbCaiiNmZQvAWcqi","pdf",2591830,12,"English","# Abstract\n# Introduction\n# Materials and methods\n## Monolayer cell culture conditions","[{\"question\":\"What did the study demonstrate about mutant p53 under acute stress?\",\"answer\":\"Mutant p53 provided a selective growth advantage during acute environmental stress and drove a molecular transition toward a basal-like state in genetically defined pancreatic cancer organoid models.\"},{\"question\":\"How do transcriptomic analyses connect mutant p53 to pancreatic cancer subtype behavior?\",\"answer\":\"Under stress, organoids expressing mutant p53 adopted a basal-like gene expression program associated with poor prognosis, and the molecular subtype reverted to the classical subtype after conditions returned to normal.\"},{\"question\":\"Why is mutant p53 suggested as a therapeutic target for pancreatic cancer?\",\"answer\":\"Because mutant p53 exhibits context-dependent oncogenic properties that influence growth and subtype plasticity in pancreatic cancer, targeting it may offer a promising therapeutic strategy.\"}]","Mutant p53 regulates reversible subtype plasticity in pancreatic cancer | PDF",1790732998]