[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-456999-105":59,"doc-detail-456999-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","ky216-tubulin-complex-captures-vash2-to-inhibit-nsclc-metastasis","KY216-tubulin complex captures VASH2 to inhibit NSCLC metastasis","","Metastasis drives high mortality in non-small cell lung cancer (NSCLC), and the mechanism of microtubule-targeting agents (MTAs) remains unclear. KY216, a microtubule inhibitor, was used to form a crystal complex with αβ-tubulin, revealing KY216-tubulin binding to vasohibin-2 (VASH2) that restrains metastasis. The study identifies KY216-curved tubulin interaction sites, shows reduced VASH2 levels, blocks EMT, enhances VASH2–α-tubulin binding, suppresses ZEB1 activation, and promotes α-tubulin detyrosination, partially via the miR-429/VASH2/ZEB1 axis.",{"@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/ky216-tubulin-complex-captures-vash2-to-inhibit-nsclc-metastasis/456999/",{"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/ky216-tubulin-complex-captures-vash2-to-inhibit-nsclc-metastasis/456999.png","ImageObject",300,407,{"name":92,"@type":93},"Margaret","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":52},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What did the researchers find about KY216’s target in NSCLC?","Question",{"text":112,"@type":113},"KY216 formed a crystal complex with αβ-tubulin and was shown to bind vasohibin-2 (VASH2), which restrains NSCLC metastasis.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does KY216 affect EMT and ZEB1 signaling?",{"text":117,"@type":113},"KY216 decreases VASH2 levels and inhibits the epithelial-mesenchymal transition (EMT) process; it also prevents VASH2 from activating ZEB1.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does miR-429 play in the KY216 mechanism?",{"text":121,"@type":113},"KY216 increases miR-429 levels that target the 3’-UTR of VASH2 and ZEB1 transcripts, inhibiting EMT at least partially through the miR-429/VASH2/ZEB1 axis.","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},456999,1791404714,{"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":52,"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},137451207643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Article [https://doi.org/10.1038/s41467-025-66817-2](https://doi.org/10.1038/s41467-025-66817-2)  \nKY216-tubulin complex captures VASH2 to inhibit NSCLC metastasis  \nReceived: 10 April 2024  \n\n| Accepted: 14 November 2025 |\n| --- |\n| |\n| Check for updates |\n\nXiao-Yu He1,4, Cheng-Yan Liu1,4, Xin-Yu Ding 2,4 , Qing Lin1,4, Jia-Fu Leng1, Cheng-Mei Xiao1, Xin Zang1, Meng-Yue Wang1, Yong Yin 1 ,  \nLing-Yi Kong 1  & Yuan-Zheng Xia 1,3   \nMetastasis significantly impacts the mortality rate of non-small cell lung cancer (NSCLC) patients. Numerous microtubule-targeting agents (MTAs) reveal antimetastatic efficacy, but the mechanism remains unclear. In this research, we employ KY216, a microtubule inhibitor, to generate a crystal in complex with αβ-tubulin, and illustrate that the KY216-tubulin combination binds vasohibin- 2 (VASH2) to restrain NSCLC metastasis. Through crystal structure analysis, specific interaction sites between KY216 and curved tubulin are identified. KY216 decreases VASH2 levels, hindering the epithelial-mesenchymal transition (EMT) process in NSCLC. Moreover, the MTA enhances the binding of VASH2 to α-tubulin, prevents the activation of zinc finger E-box binding homolog 1 (ZEB1) by VASH2, promotes detyrosination of α-tubulin, and ultimately suppresses EMT. Additionally, KY216 elevates the levels of miR-429 to target the 3’-untranslated region (3’ UTR) of VASH2 and ZEB1 transcripts and inhibits EMT, at least partially, via the miR-429/VASH2/ZEB1 axis to block NSCLC metastasis. Overall, our investigation offers valuable insights into the roles of MTAs and VASH2 in NSCLC metastasis.  \nNon-small cell lung cancer (NSCLC) is the most prevalent form of lung cancer and a major contributor to global cancer-related mortality1. Despite advancements in prevention, detection, and medical treatment, metastasis remains the primary cause of death among NSCLC patients2. Distant metastasis, characterized by the spread of cancer cells to organs like the lungs, liver, brain, and bones through the blood or lymphatic system, presents a significant challenge in treatment and substantially reduces patient survival rates3,4. Therefore, a comprehensive investigation into the metastatic pathways and key signal transduction mechanisms of NSCLC is essential to develop drugs, improve therapeutic outcomes, and enhance the quality of life and prognosis for patients.  \nMicrotubules are essential components in eukaryotic cells, playing key roles in various cellular activities like maintaining structure,  \nsubstance transport, chromosome segregation, cell division, and motility5–7. There are two types of tubulins, α-tubulin and β-tubulin, that form heterodimers. Cancer cell growth relies on the dynamic polymerization and depolymerization of tubulin dimers8, which undergo post-translational modifications like detyrosination, acetylation, polyglutamylation, and polyadenylation. These modifications are present in tumor tissues and are linked to the epithelial-mesenchymal transition (EMT) process in cancer cells9. Targeting these dynamic processes has proven effective in developing anti-cancer drugs5,10. Microtubule-targeting agents (MTAs) are categorized as microtubule stabilizers (MSAs) like paclitaxel or microtubule destabilizers (MDAs) like colchicine and combretastatin A-4 (CA-4), based on their action11–13. These drugs disrupt cancer cell mitosis by targeting specific binding sites, leading to significant inhibition of cancer cell growth14–16.  \n1Basic Medical Research Innovation Center for Anti-Cancer Drugs, MOE and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China. 2Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 3Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor and Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University), Ministry of Education, Nanning","cbCaiteIHrGezPpl","https://ap.wps.com/l/cbCaiteIHrGezPpl","pdf",9480618,22,"English","# Background\n## NSCLC metastasis and EMT\n## Microtubules and tubulin post-translational modifications\n# Mechanistic Findings\n## KY216–tubulin crystal complex and VASH2 binding\n## Effects on VASH2 levels and EMT\n## miR-429/VASH2/ZEB1 axis\n# Significance","[{\"question\":\"What did the researchers find about KY216’s target in NSCLC?\",\"answer\":\"KY216 formed a crystal complex with αβ-tubulin and was shown to bind vasohibin-2 (VASH2), which restrains NSCLC metastasis.\"},{\"question\":\"How does KY216 affect EMT and ZEB1 signaling?\",\"answer\":\"KY216 decreases VASH2 levels and inhibits the epithelial-mesenchymal transition (EMT) process; it also prevents VASH2 from activating ZEB1.\"},{\"question\":\"What role does miR-429 play in the KY216 mechanism?\",\"answer\":\"KY216 increases miR-429 levels that target the 3’-UTR of VASH2 and ZEB1 transcripts, inhibiting EMT at least partially through the miR-429/VASH2/ZEB1 axis.\"}]","KY216-tubulin complex captures VASH2 to inhibit NSCLC metastasis | PDF",1790747950,55]