[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-382926-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-382926-en":131},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","muscarinic-receptor-agonist-induced-pix-binding-to-catenin-promotes-colon-neoplasia","Muscarinic receptor agonist-induced βPix binding to β-catenin promotes colon neoplasia","","M3 muscarinic receptor activation (M3R) modulates β-catenin signaling and contributes to colon neoplasia. βPix, a Cdc42/Rac guanine nucleotide exchange factor, binds β-catenin in colon cancer cells, enhancing β-catenin–dependent transcriptional activity. Combining in silico, in vitro, and in vivo methods, nuclear co-localization of βPix and β-catenin was observed in M3R-overexpressing cancer stem cells at invasive fronts, and M3R agonists induced time-dependent βPix–β-catenin cytoplasmic and nuclear association. βPix knockdown reduced proliferation, migration, invasion, and PTGS2 expression, while βPix overexpression increased β-catenin binding to TCF4 and attenuated advanced neoplasia in βPix conditional knockout mice.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/muscarinic-receptor-agonist-induced-pix-binding-to-catenin-promotes-colon-neoplasia/382926/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/muscarinic-receptor-agonist-induced-pix-binding-to-catenin-promotes-colon-neoplasia/382926.png","ImageObject",300,407,{"name":42,"@type":43},"supergirl","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-29","2026-09-24",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What role does M3R play in β-catenin signaling in colon cancer?","Question",{"text":63,"@type":64},"M3 muscarinic receptors modulate β-catenin signaling, and MR activation augments β-catenin transcriptional activity in colon cancer cells.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does βPix affect colon cancer cell behavior when induced by M3R?",{"text":68,"@type":64},"βPix knockdown attenuates M3R agonist-induced proliferation, migration, invasion, and reduces PTGS2 expression; βPix overexpression enhances β-catenin binding to TCF4.",{"name":70,"@type":61,"acceptedAnswer":71},"What do the in vivo βPix conditional knockout results show?",{"text":72,"@type":64},"In a murine sporadic colon cancer model, conditional knockout of βPix in intestinal epithelium attenuates advanced neoplasia and reduces β-catenin target genes and proteins such as c-Myc and Ptgs2.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},382926,1790342418,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":107,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":108,"slug":109},7,40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":112,"show_sort_weight":113,"slug":114},8,"Research & Report",30,"research-report",{"id":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},962088121634,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","[www. nature.com/scientificreports](www. nature.com/scientificreports)  \nOPEN  \nMuscarinic receptor agonist‑induced βPix binding to β‑catenin promotes colon neoplasia  \nKunrong Cheng1,2, Ahmed Chahdi2, Shannon M. Larabee3, Mazen Tolaymat2, Margaret H. Sundel 3, Cinthia B. Drachenberg4, Min Zhan5, Shien Hu1,2, Anan H. Said2, Aaron C. Shang2, Guofeng Xie1,2,6, Madeline Alizadeh7, Natalia Sampaio Moura2,  \nAndrea C. Bafford 3, RichelleT. Williams 3,6, Nader N. Hanna3,6 & Jean‑Pierre Raufman1,2,6,8*  \nM3 muscarinic receptors (M3R) modulate β‑catenin signaling and colon neoplasia. CDC42/RAC guanine nucleotide exchange factor, βPix, binds to β‑catenin in colon cancer cells, augmenting β‑catenin transcriptional activity. Using in silico, in vitro, and in vivo approaches, we explored whether  \nthese actions are regulated by M3R. Atthe invasive fronts of murine and human colon cancers, we detected co‑localized nuclear expression of βPix and β‑catenin in stem cells overexpressing M3R. Using immunohistochemistry, immunoprecipitation, proximity ligand, and fluorescent cell sorting assays in human tissues and established and primary human colon cancer cell cultures, we detected time‑dependent M3R agonist‑induced cytoplasmic and nuclear association of βPix with β‑catenin.βPix knockdown attenuated M3R agonist‑induced human colon cancer cell proliferation, migration, invasion, and expression of PTGS2, the gene encoding cyclooxygenase‑2, a key player in colon neoplasia. Overexpressing βPix dose‑dependently augmented β‑catenin binding to the transcription factor TCF4 . In a murine model of sporadic colon cancer, advanced neoplasia was attenuated in conditional knockout mice with intestinal epithelial cell deficiency of βPix. Expression levels of β‑catenin target genes and proteins relevant to colon neoplasia, including c-Myc and Ptgs2, were reduced in colon tumors from βPix‑deficient conditional knockout mice. Targeting the M3R/βPix/β‑ catenin axis may have therapeutic potential.  \nAbbreviations  \nAOM Azoxymethane  \nDSS Dextran sodium sulfate H&E Hematoxylin and eosin CKO Conditional knockout MR Muscarinic receptor  \nM1R M1 subtype muscarinic receptors  \nM3R M3 subtype muscarinic receptors  \nqPCR Quantitative real-time polymerase chain reaction RNAi RNA interference  \nSD Standard deviation  \n1VA Maryland Healthcare System, Baltimore, MD 21201, USA. 2Department of Medicine, Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 4Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 5Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 6Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA. 7The Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD 20201, USA. 8Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.*[email: jraufman@som.umaryland.edu](email: jraufman@som.umaryland.edu)  \n[www. nature.com/scientificreports/](www. nature.com/scientificreports/)  \nSE Standard error  \nWT Wild-type  \nIn quiescent intestinal epithelial cells, cytosolic β-catenin is sequestered in a multi-protein complex and targeted for degradation. In ~ 90% of colon cancers APC or β-catenin mutations destabilize β-catenin destruction complexes, freeing β-catenin to translocate to the cell nucleus. As a transcriptional coactivator ofTCF4, nuclear β-catenin induces transcription of genes that promote neoplasia, e.g., prostaglandin-endoperoxide synthase 2 [PTGS2, cyclooxygenase2 (COX2)]. In colon cancer cells, muscarinic receptor (MR) activation augments β-catenin signaling1. Of five MR subtypes, CHRM3, a conditional oncogene encoding M3R2, is overexpressed in 60–80% ","cbCaimN0bNUUQYSA","https://ap.wps.com/l/cbCaimN0bNUUQYSA","pdf",2481633,15,"English","# Abstract\n## βPix–β-catenin association and localization\n## Experimental approaches and cellular effects\n## In vivo conditional knockout findings\n## Therapeutic implications\n## Abbreviations","[{\"question\":\"What role does M3R play in β-catenin signaling in colon cancer?\",\"answer\":\"M3 muscarinic receptors modulate β-catenin signaling, and MR activation augments β-catenin transcriptional activity in colon cancer cells.\"},{\"question\":\"How does βPix affect colon cancer cell behavior when induced by M3R?\",\"answer\":\"βPix knockdown attenuates M3R agonist-induced proliferation, migration, invasion, and reduces PTGS2 expression; βPix overexpression enhances β-catenin binding to TCF4.\"},{\"question\":\"What do the in vivo βPix conditional knockout results show?\",\"answer\":\"In a murine sporadic colon cancer model, conditional knockout of βPix in intestinal epithelium attenuates advanced neoplasia and reduces β-catenin target genes and proteins such as c-Myc and Ptgs2.\"}]","Muscarinic receptor agonist-induced βPix binding to β-catenin promotes colon neoplasia | PDF",1790253066,38]