[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-331407-105":59,"doc-detail-331407-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","nedd9-is-transcriptionally-regulated-by-hdac4-and-promotes-breast-cancer-metastasis-and-macrophage-m2-polarization-via-the-faknf-b-signaling-pathway","NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway","","Background: Breast cancer remains a major health burden, yet the molecular mechanisms underlying its development and poor outcomes are not fully resolved. Results: CPTAC database analyses show NEDD9 is upregulated in breast cancer and correlates with worse prognosis. Functional studies demonstrate that NEDD9 increases tumor growth and metastasis in vitro and in vivo, induces EMT, and modulates macrophage polarization toward the pro-tumoral M2 state. Mechanistically, HDAC4 inhibition enhances H3K9 acetylation at the NEDD9 promoter, activates FAK/NF-κB signaling, increases IL-6 secretion, and promotes monocyte-to-M2-like differentiation. Conclusions: NEDD9 upregulation drives metastasis and M2 polarization, suggesting NEDD9 as a promising therapeutic target.",{"@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/nedd9-is-transcriptionally-regulated-by-hdac4-and-promotes-breast-cancer-metastasis-and-macrophage-m2-polarization-via-the-faknf-b-signaling-pathway/331407/",{"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/nedd9-is-transcriptionally-regulated-by-hdac4-and-promotes-breast-cancer-metastasis-and-macrophage-m2-polarization-via-the-faknf-b-signaling-pathway/331407.png","ImageObject",300,407,{"name":92,"@type":93},"Rowan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What evidence links NEDD9 to breast cancer prognosis?","Question",{"text":112,"@type":113},"CPTAC database analyses show NEDD9 expression is upregulated in breast cancer tissues and associated with poor prognosis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does NEDD9 affect breast cancer cells and metastasis?",{"text":117,"@type":113},"NEDD9 promotes tumor growth and metastasis in vitro and in vivo, disrupts mammary epithelial acinus formation, and triggers epithelial-mesenchymal transition.",{"name":119,"@type":110,"acceptedAnswer":120},"How is NEDD9 mechanistically regulated and what signaling pathway is involved?",{"text":121,"@type":113},"NEDD9 expression is increased by inhibiting HDAC4 activity, which enhances H3K9 acetylation at the NEDD9 promoter and activates the FAK/NF-κB signaling pathway.","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},331407,1790177620,{"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":29,"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,"preview_page_count":4},1099514067415,"https://ap-avatar.wpscdn.com/avatar/100002539d78ffe74a7?x-image-process=image/resize,m_fixed,w_180,h_180&k=1779092875211072502","Neoplasia 57 (2024) 101059  \nContents lists available at ScienceDirect  \nNeoplasia  \njournal [homepage:](homepage: www.elsevier.com/locate/neo)[ www.elsevier.com/locate/neo](homepage: www.elsevier.com/locate/neo)  \n| Original Research\u003Cbr>NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway\u003Cbr>*\u003Cbr>Wenhong Liu , Guanghua Luo\u003Cbr>Department of Radiology, The First Affiliated Hospital of University of South China, Hengyang City, 421001, Hunan Province, China |  |  | |\n| --- | --- | --- | --- |\n| A R T I C L E I N F O |  | A B S T R A C T |  |\n| Keywords: Breast cancer NEDD9 HDAC4\u003Cbr>FAK/NF-κB pathway EMTM2 macrophages |  | Background: Breast cancer is a malignancy with a generally poor prognosis. With the advancement of molecular research, we have gained deeper insights into the cellular processes that drive breast cancer development. However, the precise mechanisms remain elusive.\u003Cbr>Results: Based on the CPTAC database, we found that NEDD9 expression is up-regulated in breast cancer tissues and is associated with poor prognosis in breast cancer patients. Functional experiments showed that NEDD9 promotes tumor growth and metastasis both in vitro and in vivo. Overexpression of NEDD9 disrupts mammary epithelial acinus formation and triggers epithelial-mesenchymal transition in breast cancer cells, effects that are reversed upon NEDD9 gene silencing. Mechanistically, NEDD9 upregulates its expression by inhibiting HDAC4 activity, leading to enhanced H3K9 acetylation of the NEDD9 gene promoter and activation of the FAK/NF-κB signaling pathway. Furthermore, NEDD9 overexpression promotes IL-6 secretion, which further drives breast cancer progression. Notably, NEDD9 activation fosters the pro-tumoral M2 macrophage polarization in the tumor microenvironment. NEDD9 stimulates IL-6 secretion, polarizes monocytes towards an M2-like phenotype, and enhances BC cell invasiveness.\u003Cbr>Conclusions: These findings suggest that NEDD9 upregulation plays a pivotal role in breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling axis. Targeting NEDD9 may offer a promising therapeutic approach for breast cancer treatment. |  |\n\nIntroduction  \nBreast cancer is still a serious public health problem worldwide. It isnot only one of the most common types of cancer, but also one of the leading causes of disability and death in women [1]. According to statistics, the diagnosis rate of breast cancer will rank first among malignant tumors in 2020, which highlights its seriousness and universality [2]. The complexity of breast cancer lies in its molecular mechanism of occurrence and development [3]. Because of this complexity, breast cancer shows significant heterogeneity, which means that different breast cancer patients may have different gene and molecular characteristics. This heterogeneity poses challenges at the molecular level for the selection of treatment regimens and disease prognosis [4]. However, with the continuous deepening of molecular research, people have a deeper understanding of the cellular pathways of breast tumor development. These research advances are helpful in identifying new  \ndiagnostic markers and developing more effective treatment strategies [5]. Although some prognostic markers have been used to predict the treatment outcome of breast cancer patients, the treatment outcome of a large number of patients is still unsatisfactory. Therefore, further determination of new prognostic markers is crucial to improve the clinical prognosis of breast cancer patients.  \nEpigenetic modifications have profound effects on the regulation and function of cells, and targeted epigenetic therapy has become an attractive strategy in the field of cancer treatment [6]. Among them, post-translational modifications of histone residues, as a key epigenetic process, regulate chromatin accessibility and thereby regulate gene expression [","cbCaidUduuO4WWuG","https://ap.wps.com/l/cbCaidUduuO4WWuG","pdf",14496393,15,"English","# Introduction\n## Background of breast cancer and heterogeneity\n## Epigenetic modifications and HDAC roles\n## NEDD9 as a signaling scaffold","[{\"question\":\"What evidence links NEDD9 to breast cancer prognosis?\",\"answer\":\"CPTAC database analyses show NEDD9 expression is upregulated in breast cancer tissues and associated with poor prognosis.\"},{\"question\":\"How does NEDD9 affect breast cancer cells and metastasis?\",\"answer\":\"NEDD9 promotes tumor growth and metastasis in vitro and in vivo, disrupts mammary epithelial acinus formation, and triggers epithelial-mesenchymal transition.\"},{\"question\":\"How is NEDD9 mechanistically regulated and what signaling pathway is involved?\",\"answer\":\"NEDD9 expression is increased by inhibiting HDAC4 activity, which enhances H3K9 acetylation at the NEDD9 promoter and activates the FAK/NF-κB signaling pathway.\"}]","NEDD9 is transcriptionally regulated by HDAC4 and promotes breast cancer metastasis and macrophage M2 polarization via the FAK/NF-κB signaling pathway | PDF",1789993171,38]