[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-377963-105":59,"doc-detail-377963-en":131},{"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":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","topk-promotes-the-growth-of-esophageal-cancer-in-vitro-and-in-vivo-by-enhancing-yb1eef1a1-signal-pathway","TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway","","TOPK, a dual specificity serine/threonine kinase, is described as up-regulated in esophageal cancer and associated with poor prognosis. The study reports that TOPK and YB1 show high expression in esophageal cancer and that TOPK knockout suppresses cancer cell proliferation, with effects restored by re-expressing YB1. Mechanistically, TOPK phosphorylates YB1 at Thr 89 and Ser 209, enabling phosphorylated YB1 to bind the eEF1A1 promoter and activate transcription. This increases eEF1A1 protein and triggers the AKT/mTOR pathway; inhibition via HI-TOPK-032 reduces proliferation and tumor growth in vitro and in vivo.",{"@graph":69,"@context":123},[70,84,106],{"@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/topk-promotes-the-growth-of-esophageal-cancer-in-vitro-and-in-vivo-by-enhancing-yb1eef1a1-signal-pathway/377963/",{"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/topk-promotes-the-growth-of-esophageal-cancer-in-vitro-and-in-vivo-by-enhancing-yb1eef1a1-signal-pathway/377963.png","ImageObject",300,407,{"name":92,"@type":93},"\tJames","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What relationship between TOPK and YB1 is reported in esophageal cancer?","Question",{"text":113,"@type":114},"TOPK and YB1 are both highly expressed in esophageal cancer and correlate with poor prognosis. TOPK knockout suppresses esophageal cancer cell proliferation, and the effects are reversible by rescuing YB1 expression.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does TOPK regulate eEF1A1 expression according to the study?",{"text":118,"@type":114},"TOPK phosphorylates YB1 at Thr 89 and Ser 209. Phosphorylated YB1 then binds the eEF1A1 promoter to activate its transcription, increasing eEF1A1 protein levels.",{"name":120,"@type":111,"acceptedAnswer":121},"What is the effect of the TOPK inhibitor HI-TOPK-032?",{"text":122,"@type":114},"HI-TOPK-032 suppresses esophageal cancer cell proliferation and tumor growth by interfering with the TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},377963,1790677302,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":36},2336474466412,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","[www.nature.com/cddis](www.nature.com/cddis)  \nARTICLE OPEN   \nTOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway  \nWenjie Wu1,2,7, Jialuo Xu1,7, Dan Gao 1, Zhenliang Xie1, Wenjing Chen 1, Wenjing Li1,2, Qiang Yuan1,2, Lina Duan1,2, Yuhan Zhang1,2, Xiaoxiao Yang1,2, Yingying Chen1, Ziming Dong 1,3, Kangdong Liu 1,2,3,4,5,6 ✉ and Yanan Jiang 1,2,4,5 ✉  \n© The Author(s) 2023  \n\n|  | T-LAK-originated protein kinase (TOPK), a dual specificity serine/threonine kinase, is up-regulated and related to poor prognosis in many types of cancers. Y-box binding protein 1 (YB1) is a DNA/RNA binding protein and serves important roles in multiple cellular processes. Here, we reported that TOPK and YB1 were both highly expressed in esophageal cancer (EC) and correlated with poor prognosis. TOPK knockout effectively suppressed EC cell proliferation and these effects were reversible by rescuing YB1 expression. Notably, TOPK phosphorylated YB1 at Thr 89 (T89) and Ser 209 (S209) amino acid residues, then the phosphorylated YB1 bound with the promoter of the eukaryotic translation elongation factor 1 alpha 1 (eEF1A1) to activate its transcription. Consequently, the AKT/mTOR signal pathway was activated by up-regulated eEF1A1 protein. Importantly, TOPK inhibitor HI-TOPK-032 suppressed the EC cell proliferation and tumor growth by TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo. Taken together, our study reveals that TOPK and YB1 are essential for the growth of EC, and TOPK inhibitors may be applied to retard cell proliferation in EC. This |  |\n| --- | --- | --- |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n|  |  |  |\n| study highlights the promising therapeutic potential of TOPK as a target for treatment of EC. |  |  |\n|  | Cell Death and Disease (2023)14:364; [https://doi.org/10.1038/s41419-023-05883-0](https://doi.org/10.1038/s41419-023-05883-0) |  |\n|  |  |  |\n\nINTRODUCTION  \nThe main pathological types of esophageal cancer (EC) are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) . The prognosis for EC patients is poor with a 5-year survival rate of approximately 20% due to its aggressive metastatic feature and the lack of effective targeted therapies [1] . In the last decade, receptor tyrosine kinases (RTKs), including epidermal growth factor receptors (EGFRs) and vascular endothelial growth factor receptors (VEGFRs), are frequently used for most of the targeted therapies in several cancers [2] . However, these targeted treatments are virtually a failure in the therapeutic landscape for clinical EC patients. Therefore, it is urgent to exploit the molecular alterations and implement effective targeted treatments in esophageal cancer.  \nProteomic and phosphoproteomic analyses provide new insights into the molecular mechanisms of cancer growth and highlight the significant targets in the therapeutic landscape for cancer patients [3–5] . The key molecules of signal pathways involved in post-translational regulation may become new potential targets for EC therapeutics in the future. T-LAKoriginated protein kinase (TOPK) is a dual specificity serine/ threonine and MAPKK-like kinase. Dysregulation of TOPK plays a crucial role in the proliferation, progression, and metastasis of many cancers, such as lung cancer, prostate cancer and even leukemia [6, 7] . What’s more, accumulating evidence shows that  \nTOPK is a potential effective target for cancer-specific therapeutics by promoting cell death signaling pathways, preventing invasion, metastasis, and overcoming drug resistance [6] .  \nY-box binding protein 1 (YB1), a multi-functional oncoprotein with conserved Y-box protein family, is a DNA/RNA binding protein and plays an essential role in the progression of tumorigenesis [8] . YB1 promotes cell proliferation, metastasis, even drug resistance by dysregulating multiple cellular processes, such as DNA replication, transcription and repair,","cbCaiibX3FWvt22U","https://ap.wps.com/l/cbCaiibX3FWvt22U","pdf",6367500,16,"English","# Introduction\n## Esophageal cancer background and treatment challenges\n## Proteomic insights and rationale for targeting TOPK\n## Roles of YB1 in cancer progression and therapy\n## Prior findings on TOPK in ESCC metastasis and signaling pathways","[{\"question\":\"What relationship between TOPK and YB1 is reported in esophageal cancer?\",\"answer\":\"TOPK and YB1 are both highly expressed in esophageal cancer and correlate with poor prognosis. TOPK knockout suppresses esophageal cancer cell proliferation, and the effects are reversible by rescuing YB1 expression.\"},{\"question\":\"How does TOPK regulate eEF1A1 expression according to the study?\",\"answer\":\"TOPK phosphorylates YB1 at Thr 89 and Ser 209. Phosphorylated YB1 then binds the eEF1A1 promoter to activate its transcription, increasing eEF1A1 protein levels.\"},{\"question\":\"What is the effect of the TOPK inhibitor HI-TOPK-032?\",\"answer\":\"HI-TOPK-032 suppresses esophageal cancer cell proliferation and tumor growth by interfering with the TOPK/YB1/eEF1A1 signal pathway in vitro and in vivo.\"}]","TOPK promotes the growth of esophageal cancer in vitro and in vivo by enhancing YB1/eEF1A1 signal pathway | PDF",1790227825]