[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-352892-105":59,"doc-detail-352892-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","rank-signaling-drives-basal-cell-lineage-infidelity-leading-to-mammary-tumorigenesis","Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis","","Rank signaling regulates mammary gland development and epithelial differentiation. Although Rank is present in basal and luminal cells, its basal-specific function remains unclear. Using inducible basal-specific Rank expression with lineage tracing, increased basal Rank activity disrupts basal and luminal identities, causing luminal-like differentiation, lactation defects, and premalignant hybrid basal-derived lesions that progress to adenocarcinomas. Conversely, Rank loss reduces tumor formation but impairs cell identity. Multi-omics analyses show Rank activation drives epigenetic remodeling, linking basal Rank signatures to ductal carcinoma in situ recurrence and poor luminal breast cancer outcomes.",{"@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/rank-signaling-drives-basal-cell-lineage-infidelity-leading-to-mammary-tumorigenesis/352892/",{"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/rank-signaling-drives-basal-cell-lineage-infidelity-leading-to-mammary-tumorigenesis/352892.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":14},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does Rank signaling play in mammary epithelial differentiation?","Question",{"text":112,"@type":113},"Rank signaling regulates mammary gland development and epithelial differentiation, including maintenance of basal cell identity and proper differentiation programs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does increased basal Rank activity affect cell identities and disease progression?",{"text":117,"@type":113},"Increased basal Rank activity disrupts basal and luminal identities, producing aberrant luminal-like differentiation, lactation defects, and premalignant hybrid lesions that progress to adenocarcinomas.",{"name":119,"@type":110,"acceptedAnswer":120},"What mechanism connects Rank activation to lineage infidelity and tumors?",{"text":121,"@type":113},"Proteomic, transcriptomic, and chromatin analyses indicate that Rank activation drives epigenetic remodeling that leads to basal identity loss and tumor initiation.","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},352892,1790180848,{"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":14,"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},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Article [https://doi.org/10.1038/s41467-026-70020-2](https://doi.org/10.1038/s41467-026-70020-2)  \nRank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis  \nReceived: 12 August 2024  \n\n| Accepted: 13 February 2026 |\n| --- |\n| |\n| Check for updates |\n\nJaime Redondo-Pedraza 1, Patricia G. Santamaría1,11,  \nAlejandro Sanchez-Juan 1,11, María Jimenez 1,11, Ana Sofia Rocha2, Gonzalo Soria-Alcaide 1, José Terrón-Bautista 1, Ruth Álvarez 3, Víctor López1, Osvaldo Graña-Castro3,4, Eduardo Caleiras5,  \nPilar Ximénez-Embún 6, Helga Bergholtz 7, Heena Dalal 8,  \nG. Kenneth Gray 9, Marta Isasa 6, Therese Sørlie 7, Walid T. Khaled 8, Felipe Cortés-Ledesma 1, Christopher G. Mueller 10 &  \nEva González-Suárez 1,2   \nRank signaling regulates mammary gland development and epithelial differentiation. While Rank is expressed in both basal and luminal cells, its basalspecific role is unclear. Here, using inducible basal-specific Rank expression and lineage tracing, we show that Rank signaling regulates basal cell identity in postnatal mammary glands. Increased basal Rank activity disrupts basal and luminal identities, causing aberrant luminal-like differentiation, lactation defects, and premalignant lesions composed of hybrid basal-derived cells that progress to basal and luminal adenocarcinomas. Conversely, Rank loss reduces tumor formation and also impairs cell identity. Mechanistically, proteomic, transcriptomic, and chromatin analyses reveal that Rank activation drives epigenetic remodeling, leading to basal identity loss and tumor initiation. A basal Rank gene signature correlates with ductal carcinoma in situ recurrence, as well as poor outcomes in luminal breast cancers. Thus, basal Rank-driven lineage infidelity promotes pre-invasive lesions and transition to invasive breast cancer in females.  \nThe mammary gland (MG) is a specialized organ that develops postnatally and experiences dynamic morphological changes, from an initial expansion during puberty to subsequent cycles of growth/ regression led by oestrous and pregnancy/involution cycles. The MG is  \norganized as an epithelial bilayer comprising luminal cells (LCs) and basal cells (BCs) surrounding the LC layer. LCs are either hormonesensing cells, which express hormone receptors (Hrs), or luminal progenitors (LPs), devoid of Hrs. Embryonic MG development relies on  \n1Tumor Biology and Immunology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain. 2Oncobell, Bellvitge Biomedical Research Institute, IDIBELL, Barcelona, Spain. 3Bioinformatics Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain. 4Departamento de Ciencias Médicas Básicas, Instituto de Medicina Molecular Aplicada (IMMA-Nemesio Díez), Facultad de Medicina, Universidad San Pablo-CEU, CEU Universities, Madrid, Spain. 5Histopathology Core Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain. 6Proteomics Core Unit, Spanish National Cancer Research Center (CNIO), Madrid, Spain. 7Department of Cancer Genetics, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway. 8Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK. 9Department of Cell Biology, Harvard Medical School (HMS), Boston, MA 02115, USA. 10CNRS UPR 3572, Immunologie, Immunopathologie et Chimie Thérapeutique, Université de Strasbourg, Strasbourg, France. 11These authors contributed equally: Patricia G. Santamaría, Alejandro Sanchez-Juan, María Jimenez. e-mail: [egonzalez@cnio.es](egonzalez@cnio.es)  \nbipotent progenitors located in the basal compartment, able to give rise to LCs and BCs (reviewed in ref. 1). Upon birth, each epithelial compartment is mostly maintained by lineage-restricted progenitors (reviewed in ref. 1) . However, postnatally BCs retain the competence for bipotency, triggered under specific conditions2,3.  \nRank (receptor activator of nuclear factor kappa-B) and its ligand, Rankl, members oftheTNF (receptor) superfamily, play pivotal roles i","cbCaislDPCuf3Ugc","https://ap.wps.com/l/cbCaislDPCuf3Ugc","pdf",7689671,17,"English","# Introduction\n## Rank signaling in mammary gland development\n## Paradoxical effects in tumorigenesis\n# Results\n## Enhanced basal Rank signaling disrupts basal and luminal cell identity\n## Epigenetic remodeling and tumor initiation","[{\"question\":\"What role does Rank signaling play in mammary epithelial differentiation?\",\"answer\":\"Rank signaling regulates mammary gland development and epithelial differentiation, including maintenance of basal cell identity and proper differentiation programs.\"},{\"question\":\"How does increased basal Rank activity affect cell identities and disease progression?\",\"answer\":\"Increased basal Rank activity disrupts basal and luminal identities, producing aberrant luminal-like differentiation, lactation defects, and premalignant hybrid lesions that progress to adenocarcinomas.\"},{\"question\":\"What mechanism connects Rank activation to lineage infidelity and tumors?\",\"answer\":\"Proteomic, transcriptomic, and chromatin analyses indicate that Rank activation drives epigenetic remodeling that leads to basal identity loss and tumor initiation.\"}]","Rank signaling drives basal cell-lineage infidelity leading to mammary tumorigenesis | PDF",1790101910,43]