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During EMT, epithelial cells shift from symmetric divisions that yield differentiated daughters to self-renewing daughters; blocking cell division permits mesenchymal properties without stemness. ESRP1 is identified as a key regulator: ESRP1 downregulation during EMT depends on cell division. Overexpressing ESRP1 blocks stemness while preserving the mesenchymal program, and only EMT-induced stemness correlates with poor clinical outcome.",{"@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/emt-induced-stem-cell-and-mesenchymal-programs-can-be-decoupled-via-cell-division-and-esrp1-dependent-mechanisms/440760/",{"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/emt-induced-stem-cell-and-mesenchymal-programs-can-be-decoupled-via-cell-division-and-esrp1-dependent-mechanisms/440760.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-02","2026-09-29",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 does the study say about EMT-induced stemness versus mesenchymal programs?","Question",{"text":112,"@type":113},"The findings indicate that EMT can generate mesenchymal properties and stemness, but these two programs can be separated. Mesenchymal traits may occur without stemness when cell division is blocked.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Why is cell division important for stemness during EMT?",{"text":117,"@type":113},"The study reports that epithelial cells must undergo cell division to gain stemness during EMT. Blocking division prevents stemness acquisition even when mesenchymal properties increase.",{"name":119,"@type":110,"acceptedAnswer":120},"How does ESRP1 regulate EMT-driven stemness and prognosis?",{"text":121,"@type":113},"ESRP1 acts as a key regulator: it is downregulated during EMT in a cell-division-dependent manner. Restoring ESRP1 prevents stemness without altering the mesenchymal program, and only stemness correlates with poor clinical outcome.","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},440760,1790965580,{"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},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","iScience Article  \nEMT-induced stem cell and mesenchymal programs can be decoupled via cell division and ESRP1-dependent mechanisms  \nAuthors  \nPetra den Hollander, Maria Castaneda, Suhas V. Vasaikar,   ,  \nWilliam F. Symmans,  \nRama Soundararajan, Sendurai A. Mani  \nCorrespondence  \n[mani@brown.edu](mani@brown.edu)  \nIn brief  \nMolecular biology; Cell biology  \n• The acquisition of stemness during EMT depends on cell division  \n• The downregulation of ESRP1 during EMT, during cell division is essential for stemness  \n• Only the EMT-induced stemness and not the mesenchymal program predicts poor clinical outcome  \nden Hollander et al., 2026, iScience 29, 114284  \nJanuary 16, 2026 © 2025 The Author(s) . Published by Elsevier Inc.  \n[https://doi.org/10.1016/j.isci.2025.114284](https://doi.org/10.1016/j.isci.2025.114284)  \nll  \niScience  \nll  \nOPEN ACCESS  \nArticle  \nEMT-induced stem cell and mesenchymal programs can be decoupled via cell division  \nand ESRP1-dependent mechanisms  \nPetra den Hollander,1,8 Maria Castaneda,2 Suhas V. Vasaikar,2,9 Joanna Joyce Maddela,1,8 Claire Gould,1,8,14 Breanna R. Demestichas,1,8 Robiya Joseph,2,10 Shivangi Agarwal,3 Abhijeet P. Deshmukh,2,11 Alvina Zia,2,4 Shruti Shah,2 Tieling Zhou,2 Geraldine Raja,2,12 Paul Allegakoen,2,13 Nick A. Kuburich,1 Mika Pietila,2,15 Chunxiao Fu,2 Jeffrey Chang,5 Chad J. Creighton,6,7 William F. Symmans,2 Rama Soundararajan,2 and Sendurai A. Mani1,2,8,16,*  \n1Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA  \n2Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA  \n3Department of Pathology, University of Illinois, Chicago, IL, USA  \n4Department of Biology, Houston Christian University, Houston, TX, USA  \n5Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX, USA  \n6Department of Medicine, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA  \n7Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA  \n8Legorreta Cancer Center, Warren Alpert Medical School, Brown University, Providence, RI, USA  \n9Informatics and Computational Biology, Allen Institute for Immunology, Seattle, WA, USA  \n10Department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA  \n11Hologic, Inc, 10210 Genetic Center Dr, San Diego, CA, USA  \n12Cancer Biology, Mayo Clinic, Jacksonville, FL, USA  \n13Department of Medicine, University of California, San Francisco, San Francisco, CA, USA  \n14Cancer Biology Program, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA  \n15Present address: The Janssen Pharmaceutical Companies of Johnson & Johnson, Espoo, Uusimaa, Finland  \n16Lead contact  \n*[Correspondence:](Correspondence: mani@brown.edu)[ mani@brown.edu](Correspondence: mani@brown.edu)  \n[https://doi.org/10.1016/j.isci.2025.114284](https://doi.org/10.1016/j.isci.2025.114284)  \nSUMMARY  \nEpithelial-to-mesenchymal transition (EMT) is known to induce both stemness and mesenchymal properties, and our findings reveal that these two programs can be uncoupled. During EMT, epithelial cells transition from symmetric divisions producing differentiated daughter cells to self-renewing daughter cells. When we block cell division and induce EMT, cells gain mesenchymal properties but not stemness, suggesting the importance of cell division for gaining stemness. We identified ESRP1 as a key regulator of EMT-driven stemness, which get downregulated during EMT in a cell division-dependent manner. Overexpression of ESRP1 prevents the gain of stemness without affecting the mesenchymal program. Only the stemness and not the mesenchymal signature, induced during EMT, correlates with poor prognosis. All cancer cells with stemness properties exhibit mesenchymal properties, but not all mese","cbCaifMQiOFIhfB7","https://ap.wps.com/l/cbCaifMQiOFIhfB7","pdf",9633752,21,"English","# Summary\n# Introduction\n## EMT links to metastasis and therapy resistance\n## Stemness and mesenchymal traits during EMT\n## Role of ESRP1 and cell division in stemness acquisition","[{\"question\":\"What does the study say about EMT-induced stemness versus mesenchymal programs?\",\"answer\":\"The findings indicate that EMT can generate mesenchymal properties and stemness, but these two programs can be separated. Mesenchymal traits may occur without stemness when cell division is blocked.\"},{\"question\":\"Why is cell division important for stemness during EMT?\",\"answer\":\"The study reports that epithelial cells must undergo cell division to gain stemness during EMT. Blocking division prevents stemness acquisition even when mesenchymal properties increase.\"},{\"question\":\"How does ESRP1 regulate EMT-driven stemness and prognosis?\",\"answer\":\"ESRP1 acts as a key regulator: it is downregulated during EMT in a cell-division-dependent manner. Restoring ESRP1 prevents stemness without altering the mesenchymal program, and only stemness correlates with poor clinical outcome.\"}]","EMT-induced stem cell and mesenchymal programs can be decoupled via cell division and ESRP1-dependent mechanisms | PDF",1790693255,53]