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The study used combined in vitro and in vivo gain- and loss-of-function experiments, with mass spectrometry to identify LAD1-interacting proteins. Immunoprecipitation indicated that LAD1 drives aggressiveness by competitively binding Vimentin, blocking interaction with the E3 ubiquitin ligase MAEA, reducing K48-linked ubiquitination, and increasing Vimentin protein levels in gastric cancer cells.",{"@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/lad1-promotes-malignant-progression-by-diminishing-ubiquitin-dependent-degradation-of-vimentin-in-gastric-cancer/380420/",{"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/lad1-promotes-malignant-progression-by-diminishing-ubiquitin-dependent-degradation-of-vimentin-in-gastric-cancer/380420.png","ImageObject",300,407,{"name":92,"@type":93},"Chumphorn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-28","2026-09-24",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 is the main mechanism proposed for LAD1 in gastric cancer?","Question",{"text":112,"@type":113},"LAD1 binds Vimentin and prevents Vimentin from interacting with the E3 ubiquitin ligase MAEA, leading to reduced K48-linked ubiquitination and increased Vimentin protein levels.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How did the study assess LAD1’s role in tumor progression?",{"text":117,"@type":113},"The research employed multiple in vitro and in vivo functional gain- and loss-of-function experiments, including patient- and cell-derived xenograft tumor models.",{"name":119,"@type":110,"acceptedAnswer":120},"What clinical associations were observed with higher LAD1 expression?",{"text":121,"@type":113},"In gastric cancer tissues, LAD1 was overexpressed, and increased LAD1 expression correlated with worse disease-free survival and overall survival.","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},380420,1790392777,{"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},2336475401981,"https://ap-avatar.wpscdn.com/avatar/22000c94efd8d5204d?x-image-process=image/resize,m_fixed,w_180,h_180&k=1786935347598174694","Jiang et al. Journal of Translational Medicine (2023) 21:632  \n[https://doi.org/10.1186/s12967-023-04401-2](https://doi.org/10.1186/s12967-023-04401-2)  \nJournal of Translational Medicine  \n RESEARCH Open Access  \nLAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer  \nYingming Jiang1,2,3,5†, Yanchun Feng3,4,5†, Jintuan Huang2,3,5†, Zhenze Huang2,3,5†, Rongchang Tan2,3,5,  \nTuoyang Li2,3,5, Zijian Chen2,3,5, Xiaocheng Tang2,3,5, Jun Qiu2,3,5, Chujun Li1,3,5*, Hao Chen2,3,5* and Zuli Yang2,3,5*  \nAbstract  \nBackground Ladinin-1 (LAD1), an anchoring filament protein, has been associated with several cancer types, including cancers ofthe colon, lungs, and breast. However, it is still unclear how and why LAD1 causes gastric cancer (GC) . Methods Multiple in vitro and in vivo, functional gains and loss experiments were carried out in the current study to confirm the function of LAD1 . Mass spectrometry was used to find the proteins that interact with LAD1 . Immunoprecipitation analyses revealed the mechanism of LAD1 involved in promoting aggressiveness.  \nResults The results revealed that the LAD1 was overexpressed in GC tissues, and participants with increased LAD1 expression exhibited poorer disease-free survival (DFS) and overall survival (OS) . Functionally, LAD1 promotes cellular invasion, migration, proliferation, and chemoresistance in vivo and in vitro in the subcutaneous patient-and cellderived xenograft (PDX and CDX) tumor models. Mechanistically, LAD1 competitively bound to Vimentin, preventing it from interacting with the E3 ubiquitin ligase macrophage erythroblast attacher (MAEA), which led to a reduction in K48-linked ubiquitination of Vimentin and an increase in Vimentin protein levels in GC cells.  \nConclusions In conclusion, the current investigation indicated that LAD1 has been predicted as a possible prognostic biomarker and therapeutic target for GC due to its ability to suppress Vimentin–MAEA interaction.  \nKeywords LAD1, Gastric cancer, Vimentin, MAEA, Ubiquitination  \n†Yingming Jiang, Yanchun Feng, Jintuan Huang and Zhenze Huang contributed equally.  \n*Correspondence:  \nChujun Li[lichujun@mail.sysu.edu.cn](lichujun@mail.sysu.edu.cn)[ ](lichujun@mail.sysu.edu.cn)Hao Chen[chenhao29@mail.sysu.edu.cn](chenhao29@mail.sysu.edu.cn)[ ](chenhao29@mail.sysu.edu.cn)Zuli Yang [yangzuli@mail.sysu.edu.cn](yangzuli@mail.sysu.edu.cn)  \n1 Department of Gastrointestinal Endoscopy, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University,  \n510655 Guangzhou, China  \n2 Department of Gastric Surgery Section 2, Department of General Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University,  \n510655 Guangzhou, China  \n3 Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510655, China  \n4 Department of Clinical Laboratory, The Sixth Affiliated Hospital, Sun YatSen University, 510655 Guangzhou, China  \n5 Department of Thyroid Hernia Surgery, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong, China  \n© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit ","cbCaivaN92W1KbV7","https://ap.wps.com/l/cbCaivaN92W1KbV7","pdf",21726763,15,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Introduction\n## Overview of gastric cancer and chemoresistance\n## LAD1 biology and prior associations","[{\"question\":\"What is the main mechanism proposed for LAD1 in gastric cancer?\",\"answer\":\"LAD1 binds Vimentin and prevents Vimentin from interacting with the E3 ubiquitin ligase MAEA, leading to reduced K48-linked ubiquitination and increased Vimentin protein levels.\"},{\"question\":\"How did the study assess LAD1’s role in tumor progression?\",\"answer\":\"The research employed multiple in vitro and in vivo functional gain- and loss-of-function experiments, including patient- and cell-derived xenograft tumor models.\"},{\"question\":\"What clinical associations were observed with higher LAD1 expression?\",\"answer\":\"In gastric cancer tissues, LAD1 was overexpressed, and increased LAD1 expression correlated with worse disease-free survival and overall survival.\"}]","LAD1 promotes malignant progression by diminishing ubiquitin-dependent degradation of vimentin in gastric cancer | PDF",1790240113,38]