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Building on discovery of DCBLD1 as a LUAD risk-associated gene, the study characterizes its role and mechanism in LUAD. DCBLD1 overexpression promotes cellular transformation in bronchial epithelial cells and EGFRL858R alveolar type II organoids, while DCBLD1 deficiency suppresses LUAD initiation. Mechanistically, DCBLD1 directly interacts with EGFR, displacing PTP1B and sustaining EGFR activation.",{"@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/dcbld1-promotes-lung-tumorigenesis-by-inhibiting-ptp1b-dephosphorylation-of-egfr-research-paper/458441/",{"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/dcbld1-promotes-lung-tumorigenesis-by-inhibiting-ptp1b-dephosphorylation-of-egfr-research-paper/458441.png","ImageObject",300,407,{"name":92,"@type":93},"Putri","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-06","2026-09-30",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What role does DCBLD1 play in LUAD development and progression?","Question",{"text":112,"@type":113},"DCBLD1 overexpression promotes cellular transformation in relevant lung models, while DCBLD1 deficiency significantly suppresses LUAD initiation.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does DCBLD1 mechanistically affect EGFR signaling?",{"text":117,"@type":113},"DCBLD1 binds to EGFR and displaces the negative regulator PTP1B phosphatase, impairing EGFR dephosphorylation and sustaining activation of downstream PI3K/AKT and MAPK pathways.",{"name":119,"@type":110,"acceptedAnswer":120},"Does targeting DCBLD1 show antitumor effects beyond EGFR mutation status?",{"text":121,"@type":113},"DCBLD1 knockdown produces substantial antitumor effects in patient-derived organoid and xenograft models, reported as independent of EGFR mutation status.","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},458441,1791279648,{"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":24,"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},962085571259,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","Ivyspring  \nInternational Publisher  \nInternationalJournal of Biological Sciences  \n2026; 22(2): 684-700. doi: 10.7150/ijbs.112100  \nResearch Paper  \nDCBLD1 Promotes Lung Tumorigenesis by Inhibiting PTP1B Dephosphorylation of EGFR  \nYing Liu1, Yangyang Li1, Xiaowei Quan1,2, Jiayi Zhang1, Zhicong Wang1, Zhaoyuan Hou3, Herbert Yu4, Haipeng Liu5􀀍, Tengteng Zhu1,2􀀍, Biyun Qian1􀀍  \n1. Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.  \n2. Institute of Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.  \n3. Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.  \n4. Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu 96813, HI, USA.  \n5. Innovation and Incubation Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China.  \n􀀍 Corresponding authors: Biyun Qian, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. E-mail: [qianbiyun@sjtu.edu.cn](qianbiyun@sjtu.edu.cn); Tengteng Zhu, Hongqiao International Institute of Medicine, Shanghai Tongren Hospital and School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. E-mail: [garry86@sjtu.edu.cn](garry86@sjtu.edu.cn); Haipeng Liu, Innovation and Incubation Center, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, [China. E-mail: haipengliu@tongji.edu.cn](China. E-mail: haipengliu@tongji.edu.cn).  \n© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)). See [https://ivyspring.com/terms](https://ivyspring.com/terms) for full terms and conditions.  \nReceived: 2025.02.13; Accepted: 2025.11.01; Published: 2026.01.01  \nAbstract  \nLung adenocarcinoma (LUAD) progression involves multistep molecular pathogenesis, with many critical mediators of malignant transformation yet to be fully characterized. Building upon our previous discovery of discoidin, CUB and LCCL domain containing 1 (DCBLD1) as a novel LUAD risk-associated gene, we systematically investigated its function and underlying mechanisms in LUAD. Intriguingly, DCBLD1 overexpression promotes cellular transformation in both bronchial epithelial cells and EGFRL858R alveolar type II organoids, while its deficiency in DCBLD1-/ - mice significantly suppresses LUAD initiation. Mechanistic studies revealed that DCBLD1 drives oncogenesis through direct interaction with EGFR. Specifically, the intracellular domain of DCBLD1 competitively binds to EGFR, displacing the critical negative regulator PTP1B phosphatase. This displacement impairs EGFR dephosphorylation, leading to sustained receptor activation and subsequent hyperactivation of downstream PI3K/AKT and MAPK signaling cascades. The sustained signaling activation produces significant clinical implications for LUAD treatment. In therapeutic studies, DCBLD1 knockdown demonstrated substantial antitumor effects in both patient-derived organoid and xenograft models, independent of EGFR mutation status. These findings position DCBLD1 as a promising therapeutic target for LUAD patients, offering a potential strategy that complements current EGFR mutation-based approaches.  \nKeywords: DCBLD1, EGFR, PTP1B, lung adenocarcinoma, tumorigenesis  \nIntroduction  \nLung cancer is an aggressive malignancy characterized by high morbidity and mortality rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all cases, with lung adenocarcinoma (LUAD) being the most prevalent subtype [1] . Given the complex genetic landscape of this disease, researchers have been increasingly","cbCaifyOUNLkCNFN","https://ap.wps.com/l/cbCaifyOUNLkCNFN","pdf",6412307,17,"English","# Abstract\n# Introduction","[{\"question\":\"What role does DCBLD1 play in LUAD development and progression?\",\"answer\":\"DCBLD1 overexpression promotes cellular transformation in relevant lung models, while DCBLD1 deficiency significantly suppresses LUAD initiation.\"},{\"question\":\"How does DCBLD1 mechanistically affect EGFR signaling?\",\"answer\":\"DCBLD1 binds to EGFR and displaces the negative regulator PTP1B phosphatase, impairing EGFR dephosphorylation and sustaining activation of downstream PI3K/AKT and MAPK pathways.\"},{\"question\":\"Does targeting DCBLD1 show antitumor effects beyond EGFR mutation status?\",\"answer\":\"DCBLD1 knockdown produces substantial antitumor effects in patient-derived organoid and xenograft models, reported as independent of EGFR mutation status.\"}]","DCBLD1 Promotes Lung Tumorigenesis by Inhibiting PTP1B Dephosphorylation of EGFR - Research Paper | PDF",1790753122,43]