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In aggressive anaplastic thyroid cancer (ATC), aldehyde dehydrogenase–positive (ALDH+) cells enriched in supernumerary centrosomes tolerate centrosome amplification, supporting growth advantage. MEAP, a novel pharmacologic agent, preferentially restores centrosome microtubule nucleation in centrosome-deficient ALDH+ cells, causing pericentriolar accumulation, multipolar spindles, and selective ALDH+ elimination. In a preclinical ATC mouse model, MEAP reduces cell clustering, increases spindle multipolarity, lowers chromosomal instability, and yields robust antitumor response via NEDD9–STAT3 signaling.",{"@graph":69,"@context":121},[70,84,104],{"@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/aldh-anaplastic-thyroid-cancer-cells-show-vulnerability-to-a-pharmacologic-inducer-of-centrosome-declustering/350339/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":98,"encodingFormat":97,"isAccessibleForFree":99,"interactionStatistic":100},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/aldh-anaplastic-thyroid-cancer-cells-show-vulnerability-to-a-pharmacologic-inducer-of-centrosome-declustering/350339.png","ImageObject",300,407,{"name":92,"@type":93},"Đào","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-22",true,{"@type":101,"interactionType":102,"userInteractionCount":4},"InteractionCounter",{"@type":103},"ViewAction",{"@type":105,"mainEntity":106},"FAQPage",[107,113,117],{"name":108,"@type":109,"acceptedAnswer":110},"What problem does the study address in mitosis and cancer cells?","Question",{"text":111,"@type":112},"Excessive centrosome activation impairs bipolar spindle formation and induces cell death. The study targets ATC cells that tolerate centrosome amplification and therefore gain a growth advantage.","Answer",{"name":114,"@type":109,"acceptedAnswer":115},"How does MEAP affect ALDH+ anaplastic thyroid cancer cells?",{"text":116,"@type":112},"MEAP preferentially restores centrosome microtubule nucleation activity in centrosome-deficient ALDH+ cells, leading to pericentriolar accumulation, multipolar spindle formation, and selective elimination of the ALDH+ population.",{"name":118,"@type":109,"acceptedAnswer":119},"What mechanism links MEAP selectivity to ALDH+ cells?",{"text":120,"@type":112},"The selective activity of MEAP in ALDH+ cells involves modulation of NEDD9–STAT3 signaling, which supports a mechanistic framework for centrosome-targeted therapy.","https://schema.org",{"og:url":83,"og:type":123,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":125,"canonical":83},"index,follow",{"doc_id":127,"site_id":62},350339,1790088539,{"code":4,"msg":5,"data":130},{"doc_id":127,"user_id":131,"nickname":92,"user_avatar":132,"doc_module":4,"category_id":39,"category_name":40,"doc_title":65,"doc_description":67,"doc_content":133,"file_id":134,"file_url":135,"file_type":136,"file_size":137,"view_count":4,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":138,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":128,"read_time":143},1374402968488,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","RESEARCH ARTICLE  [https://doi.org/10.1158/2767-9764.CRC-25-0807](https://doi.org/10.1158/2767-9764.CRC-25-0807)  OPEN ACCESS  \nALDH + Anaplastic Thyroid Cancer Cells Show  Vulnerability to a Pharmacologic Inducer of Centrosome Declustering  \nHenry Guanghao Yu1, Krikor Bijian1, Jie Su1, Dominik Wernic1, and Moulay A. Alaoui-Jamali1,2  \n􀀶  \nABSTRACT  \nExcessive centrosome activation is detrimental to normal cells by hampering bipolar spindle formation during mitosis and inducing cell death. In the highly aggressive anaplastic thyroid cancer (ATC), cells expressing the aldehyde dehydrogenase–positive (ALDH+) stem cell trait are enriched in supernumerary centrosomes and tolerate centrosome amplification, which offers these cells a growth advantage. Our earlier work characterized the chromosomal instability (CIN) within this cell population, which was due to dysfunctional centrosomes manifesting as a deficiency in pericentriolar material. Here, we report a novel 2-4-morpholinoanilino-6-[(2-exo-norbornyl) amino]-purine (MEAP) that preferentially restores centrosome microtubule nucleation activity in centrosome-deficient ALDH+ ATC cells. Exposure of these cells to MEAP induced pericentriolar accumulation and microtubule nucleation activity of supernumerary centrosomes, resulting in spindle multipolarity. Consequently, MEAP was capable of preferentially eliminating ALDH+ ATC cell population, thus reducing cell spherogenesis and selfrenewal capacity. In a preclinical ATC mouse model, MEAP  \npreferentially eliminated ALDH+ cell clusters, increased the rate of spindle multipolarity, decreased CIN, and generated a robust antitumor response. Lastly, we identified that the selective activity of MEAP in ALDH+ cells involved the modulation of NEDD9–STAT3 signaling. Together, these findings support the potential of targeting centrosome amplification as an alternative therapeutic approach for aggressive ALDH+ cancers failing first-line therapeutics.  \nSignificance: This study identifies MEAP as the first selective vulnerability of ALDH+ ATC stem cells, their dysfunctional supernumerary centrosomes. Unlike broad chemotherapeutics, MEAP exploits this cancerspecific centrosome amplification by paradoxically hyperactivating them via NEDD9–STAT3 disruption, forcing multipolar mitosis and ALDH+ elimination while sparing bulk tumor cells. Validates centrosome declustering as a novel therapeutic axis for aggressive, stem-like cancers failing standard therapies, with robust in vivo efficacy and a mechanistic framework (NEDD9–STAT3–centrosome axis) for precision translation.  \nIntroduction  \nTumor cell heterogeneity, a hallmark of advanced cancers, involves the intricate interactions between tumor cells and infiltrating host immune and inflammatory cell populations within the tumor tissue microenvironment. Mounting evidence across various cancer types highlighted the presence within a tumor mass of cancer cell variants expressing stem cell markers, including high aldehyde dehydrogenase 1A1 (ALDH 1A1), the focus of this study. ALDH 1A1 is an enzyme involved in embryogenesis and  \n1Department of Oncology, Lady Davis Institute for Medical Research of the Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Canada. 2Department of Medicine, Faculty of Medicine, McGill University, Montreal, Canada.  \nH.G. Yu and K. Bijian contributed equally to this article.  \nCorresponding Authors: Moulay A. Alaoui-Jamali, Lady David Institute for Medical Research, 3755 Cotes Ste-Catherine, Montreal H3T1E2, Canada. E-mail: [moulay.alaoui-jamali@mcgill.ca](moulay.alaoui-jamali@mcgill.ca); and Krikor Bijian, [krikor.bijian@mail.mcgill.ca](krikor.bijian@mail.mcgill.ca)[ ](krikor.bijian@mail.mcgill.ca)[doi:](doi: 10.1158/2767-9764)[ 10.1158/2767-9764](doi: 10.1158/2767-9764) .CRC-25-0807  \nThis open access article is distributed under the Creative Commons Attribution 4.0 International (CC BY 4.0) license.  \n©2026 The Authors; Published by the American Asso","cbCaifNEnvVJKiZt","https://ap.wps.com/l/cbCaifNEnvVJKiZt","pdf",44099096,17,"English","# Abstract\n# Significance\n# Introduction","[{\"question\":\"What problem does the study address in mitosis and cancer cells?\",\"answer\":\"Excessive centrosome activation impairs bipolar spindle formation and induces cell death. The study targets ATC cells that tolerate centrosome amplification and therefore gain a growth advantage.\"},{\"question\":\"How does MEAP affect ALDH+ anaplastic thyroid cancer cells?\",\"answer\":\"MEAP preferentially restores centrosome microtubule nucleation activity in centrosome-deficient ALDH+ cells, leading to pericentriolar accumulation, multipolar spindle formation, and selective elimination of the ALDH+ population.\"},{\"question\":\"What mechanism links MEAP selectivity to ALDH+ cells?\",\"answer\":\"The selective activity of MEAP in ALDH+ cells involves modulation of NEDD9–STAT3 signaling, which supports a mechanistic framework for centrosome-targeted therapy.\"}]","ALDH + Anaplastic Thyroid Cancer Cells Show Vulnerability to a Pharmacologic Inducer of Centrosome Declustering | PDF",43]