[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-352671-105":59,"doc-detail-352671-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","transcriptional-factor-zmym3-promotes-hepatocellular-carcinoma-metastasis-by-upregulating-cttn-and-inducing-invadopodia-formation","Transcriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation","","Hepatocellular carcinoma (HCC) shows high invasiveness and metastatic potential, resulting in poor prognosis and limited early detection. This study examines how transcriptional factor ZMYM3 contributes to HCC invasion and metastasis using TCGA and GEO analyses, immunohistochemistry, single-cell sequencing, functional assays, and RNA sequencing. Results show ZMYM3 upregulation in HCC tissues and links to recurrence and poor survival. Mechanistically, ZMYM3 directly binds the CTTN promoter, increasing CTTN, promoting invadopodia formation and EMT, and enhancing tumor cell invasion and metastasis. ZMYM3 overexpression indicates elevated recurrence risk and worse outcomes.",{"@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/transcriptional-factor-zmym3-promotes-hepatocellular-carcinoma-metastasis-by-upregulating-cttn-and-inducing-invadopodia-formation/352671/",{"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/transcriptional-factor-zmym3-promotes-hepatocellular-carcinoma-metastasis-by-upregulating-cttn-and-inducing-invadopodia-formation/352671.png","ImageObject",300,407,{"name":92,"@type":93},"Kyle","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-09-23","2026-09-22",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 relationship does ZMYM3 have with hepatocellular carcinoma prognosis?","Question",{"text":112,"@type":113},"ZMYM3 is upregulated in HCC tissues and is associated with recurrence and poor prognosis based on TCGA/GEO analyses and immunohistochemistry.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How was ZMYM3 linked to metastatic behavior in HCC cells?",{"text":117,"@type":113},"Single-cell sequencing showed higher ZMYM3 expression in portal vein tumor thrombus, and functional assays demonstrated enhanced proliferation, invasion, and metastasis with ZMYM3 activity.",{"name":119,"@type":110,"acceptedAnswer":120},"What molecular mechanism explains how ZMYM3 promotes invasion and metastasis?",{"text":121,"@type":113},"ZMYM3 directly binds the CTTN promoter, increases CTTN expression, and thereby drives invadopodia formation and epithelial-mesenchymal transition (EMT), boosting invasive and metastatic capacity.","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},352671,1790146347,{"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":145},3985741905716,"https://ap-avatar.wpscdn.com/davatar_994ba38a5ba835b3df7d355c54d3ed8d","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nTranscriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation  \nFuling Zeng 1,2,5, Zihua Zhang 1,5, Tingting Hu1, Xin Xia1, Da-Lin Lu 3 ✉, Chen Qu 1 ✉ and Lu He 4 ✉  \n© The Author(s) 2026  \n\n|  |  |  |\n| --- | --- | --- |\n|  | Hepatocellular carcinoma (HCC) is characterized by high invasiveness and metastatic potential, leading to poor prognosis. Therefore, understanding the molecular mechanisms underlying HCC invasion and metastasis is essential for developing effective therapeutic strategies. This study investigates the role of ZMYM3 in HCC invasion and metastasis. Analysis of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, along with immunohistochemistry, revealed that ZMYM3 is upregulated in HCC tissues and associated with recurrence and poor prognosis. Single-cell sequencing data indicated higher ZMYM3 expression in portal vein tumor thrombus compared to primary lesions, suggesting its involvement in metastasis. Functional assays demonstrated that ZMYM3 enhances HCC cell proliferation, invasion, and metastasis. RNA sequencing identified that ZMYM3 promotes invadopodia formation and epithelial-mesenchymal transition (EMT) in HCC cells. Further chromatin immunoprecipitation sequencing and mechanistic studies showed that ZMYM3 directly binds to the promoter of CTTN, a key gene regulating invadopodia formation, thereby increasing its expression. This upregulation contributes to the enhanced invasive and metastatic capabilities of HCC cells. Our findings identify ZMYM3 overexpression as a predictor of high recurrence risk and poor prognosis in HCC patients. Mechanistically, ZMYM3 promotes invadopodia formation primarily through the upregulation of CTTN, thereby augmenting the invasive and metastatic potential of HCC cells. These results highlight the critical role of ZMYM3 in HCC |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  | progression and metastasis. |  |\n|  | Cell Death and Disease (2026)17:294; [https://doi.org/10.1038/s41419-026-08506-6](https://doi.org/10.1038/s41419-026-08506-6) |  |\n|  |  |  |\n\nINTRODUCTION  \nPrimary liver cancer is the sixth most common malignancy and the third leading cause of cancer-related deaths worldwide [1] . Hepatocellular carcinoma (HCC), the predominant form of liver cancer, accounts for over 75% of cases [2] . Due to its insidious onset and highly aggressive, invasive, and metastatic nature, early detection of HCC is often challenging, with many patients diagnosed at advanced stages, thus missing the window for surgical intervention [3] . Even after undergoing surgery or liver transplantation, metastasis and recurrence remain frequent [4] . Therefore, a deeper understanding of the mechanisms driving HCC invasion and metastasis is critical for developing new therapeutic strategies and targets, which could guide clinical management and improve survival outcomes for HCC patients.  \nNumerous studies have demonstrated that invadopodia play a critical role in the invasion, migration, and dissemination of HCC cells [5] . Invadopodia are dynamic, actin-rich protrusions formed at the leading edge of cells, particularly in tumor cells or other migrating and invasive cells [6] . Their formation involves cytoskeletal reorganization and the mobilization of specific proteins. Once established, invadopodia increase the surface area  \nof tumor cells, facilitating interactions with the extracellular matrix and driving outward protrusion [7] . Additionally, they secrete matrix metalloproteinases (MMP2/MMP9) and interact with cell surface receptors, leading to degradation and remodeling of the extracellular matrix. This process promotes tumor cell penetration through the basement membrane and subsequent invasion into surrounding tissues [8, 9] . Moreove","cbCaibM0G2mgfGzo","https://ap.wps.com/l/cbCaibM0G2mgfGzo","pdf",11504878,13,"English","# Introduction\n## Role of invadopodia in HCC invasion\n## EMT and invadopodia formation\n## ZMYM family background and study rationale","[{\"question\":\"What relationship does ZMYM3 have with hepatocellular carcinoma prognosis?\",\"answer\":\"ZMYM3 is upregulated in HCC tissues and is associated with recurrence and poor prognosis based on TCGA/GEO analyses and immunohistochemistry.\"},{\"question\":\"How was ZMYM3 linked to metastatic behavior in HCC cells?\",\"answer\":\"Single-cell sequencing showed higher ZMYM3 expression in portal vein tumor thrombus, and functional assays demonstrated enhanced proliferation, invasion, and metastasis with ZMYM3 activity.\"},{\"question\":\"What molecular mechanism explains how ZMYM3 promotes invasion and metastasis?\",\"answer\":\"ZMYM3 directly binds the CTTN promoter, increases CTTN expression, and thereby drives invadopodia formation and epithelial-mesenchymal transition (EMT), boosting invasive and metastatic capacity.\"}]","Transcriptional factor ZMYM3 promotes hepatocellular carcinoma metastasis by upregulating CTTN and inducing invadopodia formation | PDF",1790100728,33]