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This study investigates Fascin-1 (FSCN1) expression and function in neuroendocrine differentiation using GEO-based differential expression analyses, clinical samples, cell lines, androgen/antagonist treatments, knockdown assays, and ChIP-seq/ChIP to map androgen receptor binding. FSCN1 is upregulated during neuroendocrine differentiation, restricted to NEPC tumors, and repressed transcriptionally by activated AR, with AR antagonists relieving repression, while FSCN1 silencing impairs in vivo tumor growth.",{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/fascin-1-expression-is-associated-with-neuroendocrine-prostate-cancer-and-directly-suppressed-by-androgen-receptor-article/378499/",{"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/fascin-1-expression-is-associated-with-neuroendocrine-prostate-cancer-and-directly-suppressed-by-androgen-receptor-article/378499.png","ImageObject",300,407,{"name":92,"@type":93},"Well Done","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-30","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does Fascin-1 (FSCN1) play in neuroendocrine prostate cancer?","Question",{"text":112,"@type":113},"FSCN1 is upregulated during neuroendocrine differentiation in vitro and is restricted to NEPC tumors in human prostate cancer samples. Silencing FSCN1 further impairs in vivo tumor growth.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does androgen receptor (AR) affect FSCN1 expression?",{"text":117,"@type":113},"Androgen-activated AR downregulates FSCN1 expression and acts as a transcriptional repressor that directly suppresses FSCN1. AR antagonists alleviate this repression.",{"name":119,"@type":110,"acceptedAnswer":120},"What experimental approaches were used to determine AR binding and FSCN1 regulation?",{"text":121,"@type":113},"The study combines differential expression analyses using GEO datasets, experiments with androgen/antagonist treatments and knockdown in cell models, and chromatin immunoprecipitation assays including ChIP-seq to decipher AR binding to relevant regions.","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},378499,1790729410,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":44,"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},5909892210082,"https://ap-avatar.wpscdn.com/avatar/56001069da27c9f41e8?x-image-process=image/resize,m_fixed,w_180,h_180&k=1789614185077863061","British Journal of Cancer [www.nature.com/bjc](www.nature.com/bjc)  \nARTICLE OPEN   \nCellular and Molecular Biology  \nFascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor  \nAnthony Turpin 1,2,9, Carine Delliaux1,9, Pauline Parent1,2,10, Hortense Chevalier1,3,10, Carmen Escudero-Iriarte4,10, Franck Bonardi5, Nathalie Vanpouille1, Anne Flourens 1, Jessica Querol4, Aurélien Carnot3, Xavier Leroy1,6, Nicolás Herranz4, Tristan Lanel1,6, Arnauld Villers1,7, Jonathan Olivier1,7, Hélène Touzet8, Yvan de Launoit 1, Tian V. Tian4 and Martine Duterque-Coquillaud 1 ✉  \n© The Author(s) 2023  \n\n|  | BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated the expression and functional significance of Fascin-1 (FSCN1), a pro-metastasis actinbundling protein associated with poor prognosis of several cancers, in neuroendocrine differentiation of prostate cancer. METHODS: Differential expression analyses using Genome Expression Omnibus (GEO) database, clinical samples and cell lines were performed. Androgen or antagonist’s cellular treatments and knockdown experiments were used to detect changes in cell morphology, molecular markers, migration properties and in vivo tumour growth. Chromatin immunoprecipitation-sequencing (ChIP-Seq) data and ChIP assays were analysed to decipher androgen receptor (AR) binding.\u003Cbr>RESULTS: We demonstrated that FSCN1 is upregulated during neuroendocrine differentiation of prostate cancer in vitro, leading to phenotypic changes and NEPC marker expression. In human prostate cancer samples, FSCN1 expression is restricted to NEPC tumours. We showed that the androgen-activated AR downregulates FSCN1 expression and works as a transcriptional repressor to directly suppress FSCN1 expression. AR antagonists alleviate this repression. In addition, FSCN1 silencing further impairs in vivo tumour growth.\u003Cbr>CONCLUSION: Collectively, our findings identify FSCN1 as an AR-repressed gene Particularly, it is involved in NEPC aggressiveness |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| . .\u003Cbr>Our results provide the rationale for the future clinical development of FSCN1 inhibitors in NEPC patients. |  |  |\n|  | British Journal of Cancer (2023) 129:1903–1914; [https://doi.org/10.1038/s41416-023-02449-x](https://doi.org/10.1038/s41416-023-02449-x) |  |\n|  |  |  |\n\nBACKGROUND  \nProstate cancer (PCa) is the most common cancer in males worldwide. Early detection of the disease and local therapies, including surgical and radiation treatments, have improved the overall survival of PCa patients [1] . However, most PCa mortalities are caused by the metastatic progression of the disease [2] . Because PCa is driven by androgen through the nuclear androgen receptor (AR), androgen-deprivation therapy (ADT) alone or combined with radiotherapy or chemotherapy has been used as routine treatment. However, despite the initial high response rate to ADT, nearly all patients evolve to castrate-resistant prostate cancer (CRPC) associated with poor prognosis [3, 4] . Patients with CRPC develop resistance arising from multiple molecular mechanisms, such as increased androgen biosynthesis in the tumour microenvironment or through alterations of AR signalling, including AR mutations, constitutively active AR variants in the  \nabsence of ligands, AR gene amplifications, use of other signalling pathways or reliance on non-AR-mediated pathways [3, 5, 6] . Moreover, it has been shown that a small proportion of CRPC tumour cells acquire a neuroendocrine phenotype with neuronal marker expression, including chromogranin A (CHGA), synaptophysin (SYP) or enolase-2","cbCaim9qkPOqP725","https://ap.wps.com/l/cbCaim9qkPOqP725","pdf",3095319,12,"English","# Background\n# Methods\n# Results\n## FSCN1 regulation in neuroendocrine differentiation\n## AR-mediated repression of FSCN1\n# Conclusion","[{\"question\":\"What role does Fascin-1 (FSCN1) play in neuroendocrine prostate cancer?\",\"answer\":\"FSCN1 is upregulated during neuroendocrine differentiation in vitro and is restricted to NEPC tumors in human prostate cancer samples. Silencing FSCN1 further impairs in vivo tumor growth.\"},{\"question\":\"How does androgen receptor (AR) affect FSCN1 expression?\",\"answer\":\"Androgen-activated AR downregulates FSCN1 expression and acts as a transcriptional repressor that directly suppresses FSCN1. AR antagonists alleviate this repression.\"},{\"question\":\"What experimental approaches were used to determine AR binding and FSCN1 regulation?\",\"answer\":\"The study combines differential expression analyses using GEO datasets, experiments with androgen/antagonist treatments and knockdown in cell models, and chromatin immunoprecipitation assays including ChIP-seq to decipher AR binding to relevant regions.\"}]","Fascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor - Article | PDF",1790230333]