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This study shows that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization activates β-catenin-mediated endothelial-mesenchymal transition (EndMT), providing a mechanistic bridge between DM and colon cancer. Tumor microenvironment differences were profiled by mRNA microarrays and validated in patients and models, with signaling effects examined under high glucose and cancer cell supernatant conditions.",{"@graph":69,"@context":123},[70,84,106],{"@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/pecam-1-drives-catenin-mediated-endmt-via-internalization-in-colon-cancer-with-diabetes-mellitus/380315/",{"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/pecam-1-drives-catenin-mediated-endmt-via-internalization-in-colon-cancer-with-diabetes-mellitus/380315.png","ImageObject",300,407,{"name":92,"@type":93},"Angel","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",12,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"How does PECAM-1 contribute to EndMT in diabetes-associated colon cancer?","Question",{"text":113,"@type":114},"The study indicates that DM causes PECAM-1 to defect from the cell membrane, become internalized, and accumulate near the nucleus in endothelial cells. This promotes β-catenin entry into the nucleus, triggering EndMT in colon cancer associated with DM.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"What methods were used to compare colon cancer with and without diabetes mellitus?",{"text":118,"@type":114},"The tumor microenvironment was examined for differences using mRNA-microarray analysis. Effects of DM were assessed in clinical patients and animal models, and EndMT-related signaling was tested under high glucose and coculture/supernatant conditions using western blot and immunofluorescence.",{"name":120,"@type":111,"acceptedAnswer":121},"Which signaling pathway is reported to enhance β-catenin stability and support EndMT?",{"text":122,"@type":114},"The Akt/GSK-3β pathway is reported to be enhanced, inhibiting β-catenin degradation. This stabilization supports the β-catenin-dependent process leading to EndMT.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},380315,1790338272,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},687207412472,"https://ap-avatar.wpscdn.com/davatar_155a257f0dc6eb9ab79c44ca47cae57d","Wu et al. Cell Communication and Signaling (2023) 21:203  \n[https://doi.org/10.1186/s12964-023-01193-2](https://doi.org/10.1186/s12964-023-01193-2)  \nCell Communication and Signaling  \n RESEARCH Open Access  \nPECAM-1 drives β-catenin-mediated EndMT   via internalization in colon cancer with diabetes mellitus  \nQing Wu1†, Xingxing Du1†, Jianing Cheng1†, Xiuying Qi1, Huan Liu2, Xiaohong Lv1, Xieyang Gong3, Changxin Shao3, Muhong Wang4, Luxiao Yue1, Xin Yang1, Shiyu Li1, Yafang Zhang1*, Xuemei Li 1* and Huike Yang1*  \nAbstract  \nBackground Diabetes mellitus (DM) is considered to be a risk factor in carcinogenesis and progression,  \nalthough the biological mechanisms are not well understood. Here we demonstrate that platelet-endothelial cell adhesion molecule 1 (PECAM-1) internalization drives β-catenin-mediated endothelial-mesenchymal transition (EndMT) to link DM to cancer.  \nMethods The tumor microenvironment (TME) was investigated for differences between colon cancer with and without DM by mRNA-microarray analysis. The effect of DM on colon cancer was determined in clinical patients and animal models. Furthermore, EndMT, PECAM-1 and Akt/GSK-3β/β-catenin signaling were analyzed under high glucose (HG) and human colon cancer cell (HCCC) supernatant (SN) or coculture conditions by western and immunofluorescence tests.  \nResults DM promoted the progression and EndMT occurrence of colon cancer (CC) . Regarding the mechanism, DM induced PECAM-1 defection from the cytomembrane, internalization and subsequent accumulation around the cell nucleus in endothelial cells, which promoted β-catenin entry into the nucleus, leading to EndMT occurrence in CC with DM. Additionally, Akt/GSK-3β signaling was enhanced to inhibit the degradation of β-catenin, which regulates the process of EndMT.  \nConclusions PECAM-1 defects and/or internalization are key events for β-catenin-mediated EndMT, which is significantly boosted by enhanced Akt/GSK-3β signaling in the DM-associated TME. This contributes to the mechanism by which DM promotes the carcinogenesis and progression of CC.  \nKeywords Colon cancer, Diabetes mellitus, EndMT, PECAM-1, β-catenin  \n†Qing Wu, Xingxing Du and Jianing Cheng contributed equally to this work.  \n*Correspondence:  \nYafang Zhang [yafangzhang2008@aliyun.com](yafangzhang2008@aliyun.com)[ ](yafangzhang2008@aliyun.com)Xuemei Li [xuemeili@hrbmu.edu.cn](xuemeili@hrbmu.edu.cn)[ ](xuemeili@hrbmu.edu.cn)Huike Yang [huikeyang@hrbmu.edu.cn](huikeyang@hrbmu.edu.cn)  \nFull list of author information is available at the end of the article  \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 [http://creativecommons.org/licenses/by/4.0/](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[. The Creative Commons Public Domain Dedication waiver (](http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ()[http://creativeco](http://creativeco)[mmons.org/publicdomain/zero/1.0/](mmons.org/publicdomain/zero/1.0/)) applies to the data made available in this article, unless otherwise stated in a credit line to the data.  \nWu et al. Cell Communication and Signaling (2023) 21:203 Page 2 of 14  \nGraph","cbCaiaYQXCfE5nL3","https://ap.wps.com/l/cbCaiaYQXCfE5nL3","pdf",10839826,14,"English","# Background\n# Methods\n# Results\n# Conclusions\n# Graphical Abstract","[{\"question\":\"How does PECAM-1 contribute to EndMT in diabetes-associated colon cancer?\",\"answer\":\"The study indicates that DM causes PECAM-1 to defect from the cell membrane, become internalized, and accumulate near the nucleus in endothelial cells. This promotes β-catenin entry into the nucleus, triggering EndMT in colon cancer associated with DM.\"},{\"question\":\"What methods were used to compare colon cancer with and without diabetes mellitus?\",\"answer\":\"The tumor microenvironment was examined for differences using mRNA-microarray analysis. Effects of DM were assessed in clinical patients and animal models, and EndMT-related signaling was tested under high glucose and coculture/supernatant conditions using western blot and immunofluorescence.\"},{\"question\":\"Which signaling pathway is reported to enhance β-catenin stability and support EndMT?\",\"answer\":\"The Akt/GSK-3β pathway is reported to be enhanced, inhibiting β-catenin degradation. This stabilization supports the β-catenin-dependent process leading to EndMT.\"}]","PECAM-1 drives β-catenin-mediated EndMT via internalization in colon cancer with diabetes mellitus | PDF",1790239695,35]