[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-332144-105":59,"doc-detail-332144-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","complement-regulatory-protein-cd46-promotes-bladder-cancer-metastasis-through-activation-of-mmp9","Complement regulatory protein CD46 promotes bladder cancer metastasis through activation of MMP9","","CD46 is a transmembrane complement regulator often dysregulated in cancer, with overexpression in bladder tumors enabling resistance to complement- and antibody-mediated cytotoxicity. This study investigates a new function of CD46 in promoting invasion and metastasis by regulating matrix metalloproteases. CD46 alteration increased MMP9 expression, activated p38 MAPK and AKT, and enhanced AP-1 activity via c-Jun upregulation. Blocking p38 or AKT reduced CD46-driven MMP9 and AP-1 upregulation, indicating that CD46 promotes MMP9 through both pathways.",{"@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/complement-regulatory-protein-cd46-promotes-bladder-cancer-metastasis-through-activation-of-mmp9/332144/",{"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/complement-regulatory-protein-cd46-promotes-bladder-cancer-metastasis-through-activation-of-mmp9/332144.png","ImageObject",300,407,{"name":92,"@type":93},"Hazel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-29","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":44},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What is CD46 and why is it relevant to bladder cancer?","Question",{"text":112,"@type":113},"CD46 is a transmembrane protein that regulates complement activity and prevents complement-mediated tissue damage. The document notes that CD46 contributes to bladder cancer and that its dysregulation is linked to cancer progression.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does CD46 influence metastasis in bladder cancer cells?",{"text":117,"@type":113},"The study reports that CD46 alteration positively affects MMP9 expression and functionally increases migratory and invasive capabilities, as well as in vivo metastasis.",{"name":119,"@type":110,"acceptedAnswer":120},"Which signaling pathways mediate CD46-induced MMP9 upregulation?",{"text":121,"@type":113},"CD46 overexpression triggers phosphorylation of p38 MAPK and AKT, leading to increased AP-1 activity via c-Jun upregulation. Inhibition of p38 or AKT attenuates the CD46-induced MMP9 and AP-1 increases.","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},332144,1790122081,{"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":44,"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},137441390410,"https://ap-avatar.wpscdn.com/avatar/2000252f4ab5702993?_k=1776741390130283984","INTERNATIONAL JOURNAL OF ONCOLOGY 65: 71, 2024  \nComplement regulatory protein CD46 promotes bladder cancer metastasis through activation of MMP9  \nTHUY NGUYEN THI 1 , HIEN DUONG THANH 1 , VAN‑TAN NGUYEN2 , SE‑YOUNG KWON 1 , CHANGJONG MOON3 , EU CHANG HWANG4 and CHAEYONG JUNG 1  \n1Department of Anatomy, Chonnam National University Medical School, Gwangju 61469, Republic of Korea; 2Department of Biomedical Science, Chonnam National University Medical School, Gwangju 61469, Republic of Korea;  \n3College of Veterinary Medicine, Chonnam National University, Gwangju 61186, Republic of Korea; 4Department of Urology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea  \nReceived February 19, 2024; Accepted May 8, 2024  \nDOI: 10.3892/ijo.2024.5659  \nAbstract. CD46, a transmembrane protein known for protecting cells from complement‑mediated damage, is frequently dysregulated in various types of cancer. Its over‑ expression in bladder cancers safeguards the cancer cells against both complement and antibody‑mediated cytotoxicity. The present study explored a new role of CD46 in facilitating cancer cell invasion and metastasis, examining its regulatory effect on matrix metalloproteases (MMPs) and their effect on the metastatic capability of bladder cancer cells. Specifically, CD46 alteration positively influenced MMP9 expression, but not MMP2, in several bladder cancer cell lines. Furthermore, CD46 overexpression triggered phosphorylation ofp38 MAPK and protein kinase B (AKT), leading to enhanced activator protein 1 (AP‑1) activity via c‑Jun upregulation. The inhibition of p38 or AKT pathways attenuated the CD46‑induced MMP9 and AP‑1 upregulation, indicating that the promotion of MMP9 by CD46 involved activating both p38 MAPK and AKT.  \nCorrespondence to: Professor Chaeyong Jung, Department of Anatomy, Chonnam National University Medical School, 160  \nBaekseo‑ro, Dong‑gu, Gwangju 61469, Republic of Korea E‑mail: [chjung@jnu.ac.kr](chjung@jnu.ac.kr)  \nAbbreviations: AKT, protein kinase B; AP‑1, activator protein 1; EGFR, epidermal growth factor receptor; ELISA, enzyme‑linked immunoabsorbent assays; ERK, extracellular signal‑regulated kinases; Ets, E‑twenty six; FBS, fetal bovine serum; H&E, hematoxylin and eosin; JNK, c‑Jun N‑terminal kinases; KRT13, keratin 13; MAPK, mitogen‑activated protein kinase; MGP, matrix Gla protein; MMLV, moloney murine leukemia virus; MMP2, matrix metalloproteinase 2; MMP9, matrix metalloproteinase 9; MMPs, matrix metalloproteinases; NF‑κB, nuclear factor kappa B; PI3K, phosphatidylinositol 3‑kinase; RT‑qPCR, reverse transcription‑quantitative PCR; SP‑1, specificity protein 1; SPAK, Ste20/SPS‑1‑related kinase  \nKey words: CD46, bladder cancer, matrix metalloproteinase 9, metastasis, 5637  \nFunctionally, the upregulation of MMP9 by CD46 translated to increased migratory and invasive capabilities of bladder cancer cells, as well as enhanced in vivo metastasis. Overall, the present study revealed a novel role for CD46 as a metas‑ tasis promoter through MMP9 activation in bladder cancersand highlighted the regulatory mechanism of CD46‑mediated MMP9 promotion via p38 MAPK and AKT activation.  \nIntroduction  \nCD46, a transmembrane protein, plays pivotal roles in various biological processes, including immune activation and the modulation of adaptive immunity. Notably, it regulates complement activity, a crucial component of the immune system that targets invading pathogens and damaged cells (1) . CD46 functions as a co‑factor in the degradation of comple‑ ment components, thereby inhibiting complement activation. This inhibition is essential to prevent excessive or inappro‑ priate activation of the complement system, which could result in tissue damage and autoimmune disorders. CD46 is widely distributed in tissues, being expressed by almost all human cell populations, with the exception of erythrocytes (2) . It is commonly expressed in four distinct isoforms, resulting from alternative mRNA s","cbCaicVixqol4Eha","https://ap.wps.com/l/cbCaicVixqol4Eha","pdf",4913476,13,"English","# Abstract\n# Introduction","[{\"question\":\"What is CD46 and why is it relevant to bladder cancer?\",\"answer\":\"CD46 is a transmembrane protein that regulates complement activity and prevents complement-mediated tissue damage. The document notes that CD46 contributes to bladder cancer and that its dysregulation is linked to cancer progression.\"},{\"question\":\"How does CD46 influence metastasis in bladder cancer cells?\",\"answer\":\"The study reports that CD46 alteration positively affects MMP9 expression and functionally increases migratory and invasive capabilities, as well as in vivo metastasis.\"},{\"question\":\"Which signaling pathways mediate CD46-induced MMP9 upregulation?\",\"answer\":\"CD46 overexpression triggers phosphorylation of p38 MAPK and AKT, leading to increased AP-1 activity via c-Jun upregulation. Inhibition of p38 or AKT attenuates the CD46-induced MMP9 and AP-1 increases.\"}]","Complement regulatory protein CD46 promotes bladder cancer metastasis through activation of MMP9 | PDF",1789997017,33]