[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-372883-105":59,"doc-detail-372883-en":135},{"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":128,"head_meta":130,"extra_data":132,"updated_unix":134},105,"en","ayaptazcdc6-axis-initiates-and-maintains-malignant-transformation","AYAP/TAZ–CDC6 Axis Initiates and Maintains Malignant Transformation","","Malignant transformation drives cells to gain proliferative advantages through dysregulated signaling. YAP and TAZ, Hippo pathway effectors, are established regulators of proliferation, yet how they sustain transformation was unclear. Using an in vitro transformation system with immortalized iMEFs expressing active YAP or TAZ, the study shows hyperactivation is sufficient, and their removal reverses the transformed phenotype. Transcriptomics uncovered a 17-gene YAP signature enriched in cell-cycle genes, identifying CDC6 as a critical YAP/TAZ target. CDC6 depletion blocks anchorage-independent growth, while TCGA analyses link high YAP/TAZ activity with elevated CDC6 and a strong positive correlation across multiple tumors. These conserved axes support therapeutic targeting across cancer types.",{"@graph":69,"@context":127},[70,84,106],{"@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/ayaptazcdc6-axis-initiates-and-maintains-malignant-transformation/372883/",{"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/ayaptazcdc6-axis-initiates-and-maintains-malignant-transformation/372883.png","ImageObject",300,407,{"name":92,"@type":93},"acoobca","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",13,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119,123],{"name":110,"@type":111,"acceptedAnswer":112},"What experimental model was used to test YAP/TAZ-driven transformation?","Question",{"text":113,"@type":114},"The study used an in vitro transformation model with immortalized mouse embryonic fibroblasts (iMEFs) constitutively expressing active YAP or TAZ.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How did the researchers assess whether YAP/TAZ are required for malignant transformation maintenance?",{"text":118,"@type":114},"They showed that removing YAP or TAZ reversed the transformed phenotype, indicating necessity for both tumor initiation and maintenance.",{"name":120,"@type":111,"acceptedAnswer":121},"Why is CDC6 highlighted as a key target in the YAP/TAZ axis?",{"text":122,"@type":114},"Transcriptomic profiling identified CDC6 as a critical YAP/TAZ target, and CDC6 depletion impaired YAP/TAZ-induced anchorage-independent growth.",{"name":124,"@type":111,"acceptedAnswer":125},"What evidence links the YAP/TAZ–CDC6 axis to human cancers?",{"text":126,"@type":114},"Analysis of TCGA datasets showed elevated CDC6 expression across multiple human tumors with high YAP and TAZ activity, along with a strong positive correlation between CDC6 and YAP/TAZ expression.","https://schema.org",{"og:url":83,"og:type":129,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":131,"canonical":83},"index,follow",{"doc_id":133,"site_id":62},372883,1790645871,{"code":4,"msg":5,"data":136},{"doc_id":133,"user_id":137,"nickname":92,"user_avatar":138,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":144,"language":145,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":146,"faqs":147,"seo_title":148,"seo_description":67,"update_tm":149,"read_time":150},3985747870733,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Cancer Science  \nORIGINAL ARTICLE  OPEN ACCESS   \nAYAP/TAZ–CDC6 Axis Initiates and Maintains Malignant Transformation  \nDavid Nduru1 | Yudai Ohta1,2 | Akihiro Nita2 | Mayumi Niimura1 | Samson Ngurari1 | Toshiro Moroishi1,2   \n1Department of Molecular and Medical Pharmacology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan | 2Division of Cellular Dynamics,  \nMedical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo, Tokyo, Japan Correspondence: Toshiro Moroishi ([moroishi.toshiro@tmd.ac.jp](moroishi.toshiro@tmd.ac.jp))  \nReceived: 17 September 2025 | Revised: 6 November 2025 | Accepted: 17 November 2025  \nKeywords: cancer | CDC6 | hippo pathway | malignant transformation | TAZ | YAP  \nABSTRACT  \nMalignant transformation involves the acquisition of proliferative advantages by cells, often through the dysregulation of key signaling pathways. The Hippo pathway effectors YAP and TAZ are well-established regulators of cell proliferation, and their aberrant activation is linked to tumorigenesis in various cancers. However, the molecular mechanisms by which YAP and TAZ sustain malignant transformation remain unclear. In this study, we employed an in vitro transformation model using immortalized mouse embryonic fibroblasts (iMEFs) constitutively expressing active YAP or TAZ. We demonstrated that YAP or TAZ hyperactivation is sufficient to induce malignant transformation, and that the removal of these proteins reverses the transformed phenotype, indicating their necessity for both tumor initiation and maintenance. Transcriptomic profiling identified a 17-gene signature specifically upregulated by YAP, which was enriched in cell cycle–related genes. Among these, CDC6, a DNA replication licensing factor, emerged as a critical target of YAP and TAZ. Functional assays revealed that CDC6 depletion impaired YAP/TAZ-induced anchorage-independent growth. Moreover, analysis of The Cancer Genome Atlas (TCGA) datasets showed elevated CDC6 expression across multiple human tumors with high YAP and TAZ activity, and a strong positive correlation between CDC6 and YAP/TAZ expression. These findings highlight that the conserved YAP/TAZ–CDC6 axes are key drivers of malignant transformation and underscore their potential as therapeutic targets across diverse cancer types.  \n1 | Introduction  \nMalignant transformation in cancer is a complex process wherein proliferating cells acquire a growth advantage, primarily because of alterations in specific genes that regulate cell growth and proliferation [1] . Cancer cells exhibit hallmark characteristics such as hyperproliferation, resistance to growth suppressors and cell death, replicative immortality, angiogenesis stimulation, and invasive/metastatic potential [2, 3] . For sustained and coordinated cell survival and  \nproliferation, a cascade of complex biochemical processes known as cell signaling pathways must occur in cells and remain strictly regulated [4] . Dysregulation of these pathways, typically caused by gene mutations and aberrant protein expression or activity, can lead to altered cell survival and, in the context of cancer, a survival advantage [5] . Recent advancesin omics technologies have revealed the intricate molecular landscape underlying cancer initiation and progression (hereafter referred to as tumorigenesis), highlighting considerable variations in the genes and pathways that are altered in  \n\n| Abbreviations: CDC6, cell division cycle 6; CHOL, cholangiocarcinoma; GBM, glioblastoma; iMEFs, immortalized mouse embryonic fibroblasts; LIHC, liver hepatocellular carcinoma; OV, ovarian cancer; PAAD, pancreatic ductal adenocarcinoma; SARC, sarcoma; TAZ, transcriptional coactivator with PDZ-binding motif; TCGA, The Cancer Genome Atlas; YAP, yes-associated protein.\u003Cbr>David Nduru and Yudai Ohta authors are contributed equal to this work. |\n| --- |\n| This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDe","cbCaimWB60dzWCui","https://ap.wps.com/l/cbCaimWB60dzWCui","pdf",7470972,11,"English","# Introduction\n## Malignant transformation and signaling pathway dysregulation\n## Hippo pathway and YAP/TAZ roles in cancer\n## Study rationale","[{\"question\":\"What experimental model was used to test YAP/TAZ-driven transformation?\",\"answer\":\"The study used an in vitro transformation model with immortalized mouse embryonic fibroblasts (iMEFs) constitutively expressing active YAP or TAZ.\"},{\"question\":\"How did the researchers assess whether YAP/TAZ are required for malignant transformation maintenance?\",\"answer\":\"They showed that removing YAP or TAZ reversed the transformed phenotype, indicating necessity for both tumor initiation and maintenance.\"},{\"question\":\"Why is CDC6 highlighted as a key target in the YAP/TAZ axis?\",\"answer\":\"Transcriptomic profiling identified CDC6 as a critical YAP/TAZ target, and CDC6 depletion impaired YAP/TAZ-induced anchorage-independent growth.\"},{\"question\":\"What evidence links the YAP/TAZ–CDC6 axis to human cancers?\",\"answer\":\"Analysis of TCGA datasets showed elevated CDC6 expression across multiple human tumors with high YAP and TAZ activity, along with a strong positive correlation between CDC6 and YAP/TAZ expression.\"}]","AYAP/TAZ–CDC6 Axis Initiates and Maintains Malignant Transformation | PDF",1790195651,28]