[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-384452-105":59,"doc-detail-384452-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","polo-like-kinase-4-plk4-potentiates-anoikis-resistance-of-p53ko-mammary-epithelial-cells-inducing-a-hybrid-emt-phenotype","Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells - inducing a hybrid EMT phenotype","","Polo-like kinase 4 (Plk4) is investigated as a cancer-related regulator of cell death and epithelial plasticity, focusing on p53 knock-out (p53KO) mammary epithelial cells. Plk4 overexpression markedly potentiates resistance to anoikis, independent of its centrosome biogenesis role. This resistance correlates with induction of a stable hybrid epithelial–mesenchymal phenotype and partial dependence on P-cadherin upregulation, including effects transmitted via conditioned media and soluble P-cadherin secretion. The study supports Plk4 oncogenic function via tumor microenvironment modulation.",{"@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/polo-like-kinase-4-plk4-potentiates-anoikis-resistance-of-p53ko-mammary-epithelial-cells-inducing-a-hybrid-emt-phenotype/384452/",{"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/polo-like-kinase-4-plk4-potentiates-anoikis-resistance-of-p53ko-mammary-epithelial-cells-inducing-a-hybrid-emt-phenotype/384452.png","ImageObject",300,407,{"name":92,"@type":93},"CatatanPagi","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-28","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":8},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What effect does Plk4 overexpression have on p53KO mammary epithelial cells?","Question",{"text":112,"@type":113},"Plk4 overexpression significantly potentiates resistance to anoikis in nontumorigenic p53 knock-out mammary epithelial cells.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"Is Plk4’s anoikis-resistance activity dependent on centrosome biogenesis?",{"text":117,"@type":113},"No. The effect is independent of Plk4’s role in centriole/centrosome biogenesis.",{"name":119,"@type":110,"acceptedAnswer":120},"How does Plk4-induced anoikis resistance relate to EMT and P-cadherin?",{"text":121,"@type":113},"Plk4-induced resistance is associated with induction of a stable hybrid epithelial–mesenchymal phenotype and is partially dependent on P-cadherin upregulation.","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},384452,1790613724,{"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":8,"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":41},962090894170,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nPolo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells by inducing a hybrid EMT phenotype  \nIrina Fonseca 1,2,3 ✉, Cíntia Horta1,2,3, Ana Sofia Ribeiro2,3, Barbara Sousa2, Gaëlle Marteil4, Mónica Bettencourt-Dias 1,3 ✉ and Joana Paredes 2,3 ✉  \n© The Author(s) 2023  \n\n| | Polo-like kinase 4 (Plk4), the major regulator of centriole biogenesis, has emerged as a putative therapeutic target in cancer due to its abnormal expression in human carcinomas, leading to centrosome number deregulation, mitotic defects and chromosomal instability. Moreover, Plk4 deregulation promotes tumor growth and metastasis in mouse models and is significantly associated with poor patient prognosis. Here, we further investigate the role of Plk4 in carcinogenesis and show that its overexpression significantly potentiates resistance to cell death by anoikis of nontumorigenic p53 knock-out (p53KO) mammary epithelial cells. Importantly, this effect is independent of Plk4’s role in centrosome biogenesis, suggesting that this kinase has additional cellular functions. Interestingly, the Plk4-induced anoikis resistance is associated with the induction of a stable hybrid epithelialmesenchymal phenotype and is partially dependent on P-cadherin upregulation. Furthermore, we found that the conditioned media of Plk4-induced p53KO mammary epithelial cells also induces anoikis resistance of breast cancer cells in a paracrine way, being also partially dependent on soluble P-cadherin secretion. Our work shows, for the first time, that high expression levels of Plk4 induce anoikis resistance of both mammary epithelial cells with p53KO background, as well as of breast cancer cells exposed to their secretome, which is partially mediated through P-cadherin upregulation. These results reinforce the idea that Plk4, independently of its role in centrosome biogenesis, functions as an oncogene, by impacting the tumor microenvironment to | |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | promote malignancy. |  |\n|  |  |  |\n|  |  |  |\n|  | Cell Death and Disease (2023)14:133; [https://doi.org/10.1038/s41419-023-05618-1](https://doi.org/10.1038/s41419-023-05618-1) |  |\n|  |  |  |\n\nINTRODUCTION  \nCentrosomes are the primary microtubule-organizing center (MTOC) of dividing animal cells. Consisting of two centrioles surrounded by a pericentriolar matrix (PCM), they participate inessential cellular processes, such as cell division, signaling, migration, and polarity [1, 2] . Centriole biogenesis is tightly regulated and occurs once per cell cycle, in S-phase, during which centrioles duplicate to ensure the assembly of a bipolar spindle in mitosis, an essential structure for proper chromosome segregation [2–5] .  \nPolo-like kinase 4 (Plk4), is a regulator of centriole biogenesis that is required for centriole duplication [5–8] via the phosphorylation and interaction with different centriolar proteins. In consequence, when Plk4 is overexpressed, it leads to centrosome amplification (CA, i.e., the presence of supernumerary centrosomes) resulting in cells with more than 4 centrioles [9], promoting genomic instability and tumorigenesis [10–15] . In fact, Plk4 overexpression, as well as CA and centrosome structure abnormalities, have been already found in many types of tumors [14–19] and shown to be significantly associated with poor clinical outcomes for cancer patients [18, 20–22] .  \nDespite strong evidence of Plk4’s role in cancer and its therapeutic potential, it is still unclear how it contributes to  \ntumorigenesis. Plk4 has been demonstrated to enhance cell migration through RhoA activation and to be associated with the expression of matrix metalloproteinases (MMPs) and other promotility genes [23] . In addition, Plk4 has been shown to promote cancer metastasis through the ","cbCaib4ZazLXW0MN","https://ap.wps.com/l/cbCaib4ZazLXW0MN","pdf",3253812,12,"English","# Introduction\n## Centrosomes and centriole biogenesis\n## Plk4 roles in cancer and tumor progression\n## p53 loss and EMT mechanisms","[{\"question\":\"What effect does Plk4 overexpression have on p53KO mammary epithelial cells?\",\"answer\":\"Plk4 overexpression significantly potentiates resistance to anoikis in nontumorigenic p53 knock-out mammary epithelial cells.\"},{\"question\":\"Is Plk4’s anoikis-resistance activity dependent on centrosome biogenesis?\",\"answer\":\"No. The effect is independent of Plk4’s role in centriole/centrosome biogenesis.\"},{\"question\":\"How does Plk4-induced anoikis resistance relate to EMT and P-cadherin?\",\"answer\":\"Plk4-induced resistance is associated with induction of a stable hybrid epithelial–mesenchymal phenotype and is partially dependent on P-cadherin upregulation.\"}]","Polo-like kinase 4 (Plk4) potentiates anoikis-resistance of p53KO mammary epithelial cells - inducing a hybrid EMT phenotype | PDF",1790263360]