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Mechanistically, Kremen2 maintains EGFR protein levels by preventing SOCS3-mediated ubiquitination and degradation, activating PI3K-AKT and JAK2-STAT3 pathways.",{"@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/kremen2-drives-the-progression-of-non-small-cell-lung-cancer-research-paper-summary/383675/",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/kremen2-drives-the-progression-of-non-small-cell-lung-cancer-research-paper-summary/383675.png","ImageObject",300,407,{"name":42,"@type":43},"Aurelia","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",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What question does the study investigate about Kremen2 in NSCLC?","Question",{"text":63,"@type":64},"It examines whether Kremen2 contributes to NSCLC progression and clarifies the underlying molecular mechanism involved in tumor growth and metastasis.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How did the researchers assess the relationship between Kremen2 and NSCLC?",{"text":68,"@type":64},"They analyzed public databases and clinical tissue samples for expression correlation, then evaluated cell proliferation and migration with colony formation, EdU, Transwell, and wound healing assays.",{"name":70,"@type":61,"acceptedAnswer":71},"What mechanism links Kremen2 to EGFR and downstream signaling?",{"text":72,"@type":64},"Kremen2 interacts with SOCS3 to prevent SOCS3-mediated ubiquitination and degradation of EGFR, promoting activation of PI3K-AKT and JAK2-STAT3 pathways.","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},383675,1790467634,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":127,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":144},1099514068365,"https://ap-avatar.wpscdn.com/avatar/10000253d8d9f28188e?_k=1776742907772140068","Sun et al. J Exp Clin Cancer Res (2023) 42:140 [https://doi.org/10.1186/s13046-023-02692-3](https://doi.org/10.1186/s13046-023-02692-3)  \nJournal of Experimental & Clinical Cancer Research  \n RESEARCH Open Access  \nKremen2 drives the progression of non-small   cell lung cancer by preventing SOCS3-mediated degradation of EGFR  \nYuxiao Sun1, Yu Gao1, Mingxin Dong1, Jiuzhen Li2,3, Xin Li2,3, Ningning He1, Huijuan Song1, Manman Zhang1, Kaihua Ji1, Jinhan Wang1, Yeqing Gu1, Yan Wang1, Liqing Du1, Yang Liu1, Qin Wang1, Hezheng Zhai1,4, Daqiang Sun2,3*, Qiang Liu1* and Chang Xu1*  \nAbstract  \nBackground The transmembrane receptor Kremen2 has been reported to participate in the tumorigenesis and metastasis of gastric cancer. However, the role of Kremen2 in non-small cell lung cancer (NSCLC) and the underlying mechanism remain unclear. This study aimed to explore the biological function and regulatory mechanism of Kremen2 in NSCLC.  \nMethods The correlation between Kremen2 expression and NSCLC was assessed by analyzing the public database and clinical tissue samples. Colony formation and EdU assays were performed to examine cell proliferation. Transwelland wound healing assays were used to observe cell migration ability. Tumor-bearing nude mice and metastatic tumor models were used to detect the in vivo tumorigenic and metastatic abilities ofthe NSCLC cells. An immunohistochemical assay was used to detect the expression of proliferation-related proteins in tissues. Western blot, immunoprecipitation and immunofluorescence were conducted to elucidate the Kremen2 regulatory mechanisms in NSCLC. Results Kremen2 was highly expressed in tumor tissues from NSCLC patients and was positively correlated with a poor patient prognosis. Knockout or knockdown of Kremen2 inhibited cell proliferation and migration ability of NSCLC cells. In vivo knockdown of Kremen2 inhibited the tumorigenicity and number of metastatic nodules of NSCLC cells in nude mice. Mechanistically, Kremen2 interacted with suppressor of cytokine signaling 3 (SOCS3) to maintain the epidermal growth factor receptor (EGFR) protein levels by preventing SOCS3-mediated ubiquitination and degradation of EGFR, which, in turn, promoted activation of the PI3K-AKT and JAK2-STAT3 signaling pathways.  \nConclusions Our study identified Kremen2 as a candidate oncogene in NSCLC and may provide a potential target for NSCLC treatment.  \nKeywords Kremen2, Non-small cell lung cancer, EGFR, SOCS3, Ubiquitination  \n*Correspondence: Daqiang Sun [sdqmd@163.com](sdqmd@163.com)[ ](sdqmd@163.com)Qiang Liu [liuqiang@irm-cams.ac.cn](liuqiang@irm-cams.ac.cn)[ ](liuqiang@irm-cams.ac.cn)Chang Xu [xuchang@irm-cams.ac.cn](xuchang@irm-cams.ac.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/","cbCaieFGcr4o82Wu","https://ap.wps.com/l/cbCaieFGcr4o82Wu","pdf",5198333,"English","# Abstract\n## Background\n## Methods\n## Results\n## Conclusions\n# Main text: study background and context\n## NSCLC epidemiology and treatment challenge\n## Kremen2 biology and prior cancer evidence","[{\"question\":\"What question does the study investigate about Kremen2 in NSCLC?\",\"answer\":\"It examines whether Kremen2 contributes to NSCLC progression and clarifies the underlying molecular mechanism involved in tumor growth and metastasis.\"},{\"question\":\"How did the researchers assess the relationship between Kremen2 and NSCLC?\",\"answer\":\"They analyzed public databases and clinical tissue samples for expression correlation, then evaluated cell proliferation and migration with colony formation, EdU, Transwell, and wound healing assays.\"},{\"question\":\"What mechanism links Kremen2 to EGFR and downstream signaling?\",\"answer\":\"Kremen2 interacts with SOCS3 to prevent SOCS3-mediated ubiquitination and degradation of EGFR, promoting activation of PI3K-AKT and JAK2-STAT3 pathways.\"}]","Kremen2 drives the progression of non-small cell lung cancer - Research paper summary | PDF",1790258715,48]