[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382183-105":59,"doc-detail-382183-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","the-aryl-sulfonamide-indisulam-inhibits-gastric-cancer-cell-migration-promoting-the-ubiquitination-and-degradation-of-the-transcription-factor-zeb1","The aryl sulfonamide indisulam inhibits gastric cancer cell migration - promoting the ubiquitination and degradation of the transcription factor ZEB1","","Aryl sulfonamide indisulam suppresses gastric cancer cell migration by promoting ubiquitination and proteasomal degradation of the transcription factor ZEB1. The study shows that indisulam markedly attenuates N-cadherin, a key epithelial-to-mesenchymal transition and migration marker. Label-free quantitative proteomics, bioinformatics, and biochemical assays demonstrate that indisulam enhances ZEB1 interaction with DCAF15, a CRL4 E3 ubiquitin ligase substrate receptor, resulting in increased ZEB1 ubiquitination and reduced migration in a ZEB1-dependent manner. Patient datasets indicate high ZEB1 mRNA associates with poorer survival, and indisulam treatment lowers ZEB1 protein levels in gastric tumor samples.",{"@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/the-aryl-sulfonamide-indisulam-inhibits-gastric-cancer-cell-migration-promoting-the-ubiquitination-and-degradation-of-the-transcription-factor-zeb1/382183/",{"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/the-aryl-sulfonamide-indisulam-inhibits-gastric-cancer-cell-migration-promoting-the-ubiquitination-and-degradation-of-the-transcription-factor-zeb1/382183.png","ImageObject",300,407,{"name":92,"@type":93},"Patrick","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What cellular process does indisulam inhibit in gastric cancer?","Question",{"text":112,"@type":113},"Indisulam inhibits gastric cancer cell migration by targeting molecular pathways that control EMT-associated migration programs.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does indisulam affect ZEB1?",{"text":117,"@type":113},"Indisulam promotes ZEB1 ubiquitination and proteasomal degradation, which reduces ZEB1 protein levels and suppresses migration in a ZEB1-dependent manner.",{"name":119,"@type":110,"acceptedAnswer":120},"What role does DCAF15 play in the mechanism?",{"text":121,"@type":113},"Indisulam enhances the interaction between ZEB1 and DCAF15, a substrate receptor of the CRL4 E3 ubiquitin ligase complex, enabling efficient ZEB1 ubiquitination.","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},382183,1790750943,{"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":39,"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},549758146520,"https://ap-avatar.wpscdn.com/avatar/80002397d8c0411e94?_k=1775819394049821470","RESEARCH ARTICLE  \nThe aryl sulfonamide indisulam inhibits gastric cancer cell migration by promoting the ubiquitination and degradation of the transcription factor ZEB1  \nReceived for publication, October 3, 2022, and in revised form, January 20, 2023 Published, Papers in Press, February 15, 2023, [https://doi.org/10.1016/j.jbc.2023.103025](https://doi.org/10.1016/j.jbc.2023.103025)  \nJiaqi Lu 1, Dan Li 1, Honglv Jiang 1, Yue Li 1, Chengpiao Lu 1, Tao Chen2, Yuhong Wang3, Xiaohui Wang 1, Wenzhao Sun 1, Zhongjian Pu4, Chunhua Qiao5, Jingjing Ma6, *, and Guoqiang Xu 1, *  \nFrom the 1Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Key Laboratory of Drug Research for Prevention and Treatment of Hyperlipidemic Diseases, Soochow University, Suzhou, Jiangsu, China; 2Department of General Surgery and 3Department of Pathology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; 4Department of Oncology, Haian Hospital of Traditional Chinese Medicine, Haian, Jiangsu, China; 5College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China; 6Department of Pharmacy, Medical Center of Soochow University, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China  \nReviewed by members of the JBC Editorial Board. Edited by Brian Strahl  \nGastric cancer is one of the cancers with high morbidity and mortality worldwide. The aryl sulfonamide indisulam inhibits the proliferation of several types of cancer cells through its function as a molecular glue to promote the ubiquitination and degradation of RNA-binding motif protein 39 (RBM39). However, it is unknown whether and how indisulam regulates the migration of cancer cells. In this work, using label-free quantitative proteomics, we discover that indisulam significantly attenuates N-cadherin, a marker for epithelial tomesenchymal transition and migration of cancer cells. Our bioinformatics analysis and biochemical experiments reveal that indisulam promotes the interaction between the zinc finger E-box-binding homeobox 1 (ZEB1), a transcription factor of N-cadherin, and DCAF15, a substrate receptor of CRL4 E3 ubiquitin ligase, and enhances ZEB1 ubiquitination and proteasomal degradation. In addition, our cell line–based experiments demonstrate that indisulam inhibits the migration of gastric cancer cells in a ZEB1-dependent manner. Analyses of patient samples and datasets in public databases reveal that tumor tissues from patients with gastric cancer express high ZEB1 mRNA and this high expression reduces patient survival rate. Finally, we show that treatment of gastric tumor samples with indisulam significantly reduces ZEB1 protein levels. Therefore, this work discloses a new mechanism by which indisulam inhibits the migration of gastric cancer cells, indicating that indisulam exhibits different biological functions through distinct signaling molecules.  \nGastric cancer is among the five types of cancers that have the highest morbidity and mortality (1). Although the treatment for gastric cancer has been improved significantlyin the past decades  \n* For correspondence: Guoqiang Xu, [gux2002@suda.edu.cn](gux2002@suda.edu.cn); Jingjing Ma, [jingjingmajj@suda.edu.cn](jingjingmajj@suda.edu.cn).  \n(2), the overall patient survival rate is still not satisfactory due to metastasis, drug resistance, side reaction, etc. (3). Inhibition of proliferation, migration, and invasion of cancer cells is an important strategy for cancer treatment. Therefore, identifying molecules that regulate these processes or elucidating the mechanism ofaction ofanticancer drugs could help us to develop new therapeutic strategies for targeted cancer treatment.  \nEpithelial to mesenchymal transition (EMT) is associated with the metastasis of ma","cbCaidvvSKSX2xRy","https://ap.wps.com/l/cbCaidvvSKSX2xRy","pdf",5351689,15,"English","# Research article background\n## Disisulam’s effect on cancer proliferation and migration\n# Mechanistic discovery\n## Proteomics and bioinformatics findings\n## ZEB1–DCAF15 interaction and ubiquitination\n# Experimental validation\n## Cell line migration assays\n## Patient datasets and sample analysis\n# Conclusion and biological implications\n## Indisulam’s mechanism through distinct signaling molecules","[{\"question\":\"What cellular process does indisulam inhibit in gastric cancer?\",\"answer\":\"Indisulam inhibits gastric cancer cell migration by targeting molecular pathways that control EMT-associated migration programs.\"},{\"question\":\"How does indisulam affect ZEB1?\",\"answer\":\"Indisulam promotes ZEB1 ubiquitination and proteasomal degradation, which reduces ZEB1 protein levels and suppresses migration in a ZEB1-dependent manner.\"},{\"question\":\"What role does DCAF15 play in the mechanism?\",\"answer\":\"Indisulam enhances the interaction between ZEB1 and DCAF15, a substrate receptor of the CRL4 E3 ubiquitin ligase complex, enabling efficient ZEB1 ubiquitination.\"}]","The aryl sulfonamide indisulam inhibits gastric cancer cell migration - promoting the ubiquitination and degradation of the transcription factor ZEB1 | PDF",1790249444,38]