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Findings Excess PLK4 is expelled via migrasomes through TSPAN6-mediated targeting, linking this pathway to mitotic failure and therapeutic vulnerability in PLK4-high tumors.",{"@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/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/migrasome-mediated-clearance-of-excess-plk4-defines-a-targetable-vulnerability/352773/",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/migrasome-mediated-clearance-of-excess-plk4-defines-a-targetable-vulnerability/352773.png","ImageObject",300,407,{"name":42,"@type":43},"Taylor Morgan","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-22",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",13,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What problem does the study address about PLK4 in cancer cells?","Question",{"text":63,"@type":64},"PLK4 overexpression can drive tumor initiation, but sustained PLK4 accumulation harms cancer cell viability. The study investigates how cancer cells clear excess PLK4 beyond proteasomal degradation.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do the authors show that migrasomes clear excess PLK4?",{"text":68,"@type":64},"The study identifies TSPAN6 as a high-affinity binder of PLK4 and shows PLK4 is incorporated into migrasomes for extracellular release, indicating a migrasome-mediated clearance mechanism.",{"name":70,"@type":61,"acceptedAnswer":71},"Why is targeting TSPAN6 considered therapeutically relevant?",{"text":72,"@type":64},"TSPAN6 knockdown blocks PLK4 expulsion, causing multipolar spindle formation, apoptosis, and reduced tumor growth and metastasis in vivo, suggesting a vulnerability in PLK4-high tumors.","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},352773,1790165343,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":128,"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},1099523885336,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","Articles  \nMigrasome-mediated clearance of excess PLK4 defines atargetable vulnerability  \nJihong Ma,a,b,c,d,e,j Yuhan Guo,a,b,c,d,e,j Yuening Jiang,a Qilong Wang,f Meiyu Bi,a Tianzhen Wang,a Yinan Xiao,a Na Zhang,a Pan Wang,a Yu Wu,a Bingteng Xie,g Gang Wang,h,i and Mo Lia,b,c,d,e,∗  \naState Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China  \nbNational Clinical Research Center for Obstetrics and Gynecology, Third Hospital, Academy for Advanced Interdisciplinary Studies, Peking University Medical and Health Analysis Center, Peking University, 100871, Beijing, China  \ncKey Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing, 100191, China  \ndBeijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology (Peking University Third Hospital), Beijing, 100191, China  \neDepartment of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China  \nfCenter of Medical and Health Analysis, Peking University Health Science Center, Beijing, 100191, China  \ngKey Laboratory of Molecular Medicine and Biological Diagnosis and Treatment (Ministry of Industry and Information Technology), School of Life Science, Beijing Institute of Technology, Beijing, 100081, China  \nhState Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing, China iCenter for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China  \nSummary  \nBackground Centrosome amplification caused by Polo-like kinase 4 (PLK4) overexpression promotes tumour initiation, yet sustained PLK4 accumulation is detrimental to cancer cell viability. While proteasomal degradation limits PLK4 levels, whether alternative clearance mechanisms exist remains unknown.  \nMethods We established inducible PLK4-overexpressing breast cancer cells and employed live-cell imaging, vesicular marker profiling, immunoprecipitation–mass spectrometry, and in vivo patient-derived xenograft models to investigate how cancer cells eliminate excess PLK4 .  \nFindings In this study, we identified a previously unrecognised mechanism in which excess PLK4 is rapidly expelled via migrasomes. The tetraspanin protein TSPAN6 directly binds PLK4 with high affinity and mediates its incorporation into migrasomes for extracellular release. In breast cancer samples, PLK4 expression decreased while TSPAN6 increased during progression. TSPAN6 knockdown blocked PLK4 expulsion, leading to multipolar spindle formation, apoptosis, and suppression of tumour growth and metastasis in vivo.  \nInterpretation Migrasome-mediated clearance represents a non-proteasomal pathway maintaining centrosome homoeostasis in cancer cells. Targeting TSPAN6 to prevent PLK4 elimination selectively triggers mitotic catastrophe in PLK4-high tumours, highlighting a previously unrecognised therapeutic vulnerability.  \nFunding This work was supported by the National Natural Science Foundation of China (NSFC) (T2225006, T2488301, and 82272948 to ML), Beijing Municipal Natural Science Foundation (Key program Z220011 to ML, 5254051 to TW), NSFC (82371640 to BX, 82403693 to PW), and the “Clinic + X” program of Peking University (to PW) .  \nCopyright © 2026 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)).  \nKeywords: PLK4; Centriole; Migrasome; Extracellular microenvironment; Breast cancer  \n*Corresponding author. State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, China.  \nE-mail address: [limo@hsc.pku.edu.cn](limo@hsc.pku.edu.cn) (M. Li).  \njThese author","cbCaipoc5kbQLmJP","https://ap.wps.com/l/cbCaipoc5kbQLmJP","pdf",10389315,"English","# Summary\n## Background\n## Methods\n## Findings\n## Interpretation\n## Funding\n# Research in context\n## Evidence before this study\n## Added value of this study\n## Implications of all the available evidence\n# Introduction","[{\"question\":\"What problem does the study address about PLK4 in cancer cells?\",\"answer\":\"PLK4 overexpression can drive tumor initiation, but sustained PLK4 accumulation harms cancer cell viability. The study investigates how cancer cells clear excess PLK4 beyond proteasomal degradation.\"},{\"question\":\"How do the authors show that migrasomes clear excess PLK4?\",\"answer\":\"The study identifies TSPAN6 as a high-affinity binder of PLK4 and shows PLK4 is incorporated into migrasomes for extracellular release, indicating a migrasome-mediated clearance mechanism.\"},{\"question\":\"Why is targeting TSPAN6 considered therapeutically relevant?\",\"answer\":\"TSPAN6 knockdown blocks PLK4 expulsion, causing multipolar spindle formation, apoptosis, and reduced tumor growth and metastasis in vivo, suggesting a vulnerability in PLK4-high tumors.\"}]","Migrasome-mediated clearance of excess PLK4 defines a targetable vulnerability | PDF",1790101335,48]