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The HGF/c-MET signaling pathway is highlighted as a key regulator in NSCLC, yet its contribution to remodeling the tumor microenvironment (TME) remains insufficiently characterized. This review summarizes how HGF/c-MET functions across normal and cancer cells, focusing on proliferation, migration, invasion, angiogenesis, and immune evasion, and it also reviews MET-targeted therapies and future directions such as new MET inhibitors and combination immunotherapy.",{"@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/unveiling-the-role-of-hgfc-met-signaling-in-non-small-cell-lung-cancer-tumor-microenvironment-read-online-free/328678/",{"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/unveiling-the-role-of-hgfc-met-signaling-in-non-small-cell-lung-cancer-tumor-microenvironment-read-online-free/328678.png","ImageObject",300,407,{"name":92,"@type":93},"Asher","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":34},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What signaling pathway is the focus of this review in NSCLC?","Question",{"text":112,"@type":113},"The review focuses on the HGF/c-Met signaling pathway and its roles in NSCLC tumor microenvironment remodeling.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How does HGF/c-MET contribute to NSCLC tumor progression?",{"text":117,"@type":113},"It contributes to tumor cell proliferation, migration, invasion, angiogenesis, and immune evasion, acting in both normal and cancer cells.",{"name":119,"@type":110,"acceptedAnswer":120},"What do MET-targeted therapies aim to address in NSCLC?",{"text":121,"@type":113},"MET-targeted therapies aim to counter NSCLC driven by MET alterations and to improve clinical outcomes, including in contexts such as MET exon 14 skipping or MET amplification.","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},328678,1790998709,{"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":34,"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},687197207639,"https://ap-avatar.wpscdn.com/davatar_a8503ba1806abce46bf441b54a3ca4cd","Review  \nUnveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment  \nShuxi Yao , Xinyue Liu, Yanqi Feng, Yiming Li, Xiangtian Xiao, Yuelin Han and Shu Xia *  \nCitation: Yao, S.; Liu, X.; Feng, Y.; Li, Y.; Xiao, X.; Han, Y.; Xia, S. Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment. Int. J. Mol. Sci. 2024, 25, 9101. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/ijms25169101](10.3390/ijms25169101)  \nAcademic Editor: Alain Couvineau  \nReceived: 28 July 2024  \nRevised: 15 August 2024  \nAccepted: 19 August 2024  \nPublished: 22 August 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \nDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and  \nTechnology, Wuhan 430030, China; [yaoshuxi@hust.edu.cn](yaoshuxi@hust.edu.cn) (S.Y.); [liuxinyuedoctor01@hust.edu.cn](liuxinyuedoctor01@hust.edu.cn) (X.L.);  \n[d202382250@hust.edu.cn](d202382250@hust.edu.cn) (Y.F.); [d202282140@hust.edu.cn](d202282140@hust.edu.cn) (Y.L.); [m202376505@hust.edu.cn](m202376505@hust.edu.cn) (X.X.);  \n[u201910354@hust.edu.cn](u201910354@hust.edu.cn) (Y.H.)  \n* Correspondence: [xiashutj@hust.edu.cn](xiashutj@hust.edu.cn)  \nAbstract: Non-small cell lung cancer (NSCLC) is characterized by several molecular alterations that contribute to its development and progression. These alterations include the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), human epidermal growth factor receptor 2 (HER2), and mesenchymal–epithelial transition factor (c-MET) . Among these, the hepatocyte growth factor (HGF)/c-MET signaling pathway plays a crucial role in NSCLC. In spite of this, the involvement of the HGF/c-MET signaling axis in remodeling the tumor microenvironment (TME) remains relatively unexplored. This review explores the biological functions of the HGF/c-MET signaling pathway in both normal and cancerous cells, examining its multifaceted roles in the NSCLC tumor microenvironment, including tumor cell proliferation, migration and invasion, angiogenesis, and immune evasion. Furthermore, we summarize the current progress and clinical applications of MET-targeted therapies in NSCLC and discuss future research directions, such as the development of novel MET inhibitors and the potential of combination immunotherapy.  \nKeywords: HGF; c-MET; tumor microenvironment; immunotherapy; NSCLC  \n1. Introduction  \nGlobally, lung cancer is the leading cause of cancer-related deaths. NSCLC accounts for 80% of all lung cancers and typically has a poor prognosis [1] . Due to the significant genetic and cellular heterogeneity of NSCLC [2], determining a tumor’s histological type and associated molecular changes is crucial for optimizing treatment. Oncogenic alterations in EGFR, ALK, MET, and other kinases drive NSCLC development [3] . Previous studies have confirmed that MET is a significant driver of mutation in NSCLC, activating signaling pathways downstream of PI3K/AKT, Ras-MAPK, and STAT3 (signal transducer and activator of transcription 3), which promote cancer proliferation, migration, and invasion [4] . Furthermore, MET amplification contributes to EGFR-TKI resistance [5] . The implementation of MET inhibition in the clinical management of NSCLC represents an increasingly significant area of research. Several MET inhibitors have been developed that that demonstrate considerable anti-tumor efficacy, particularly in cases with MET exon 14 skipping mutations (METex14) or MET amplification [6] . In the GEOMETRY mono-1 clinical trial, capmatinib (MET TKI) demonstrated clinically meaningful activity, achieving an ove","cbCaimminpOFfsBf","https://ap.wps.com/l/cbCaimminpOFfsBf","pdf",1154168,28,"English","# Introduction\n## MET signaling in NSCLC development and resistance\n# Tumor microenvironment and immunosuppression\n## Role of c-MET and HGF in the TME","[{\"question\":\"What signaling pathway is the focus of this review in NSCLC?\",\"answer\":\"The review focuses on the HGF/c-Met signaling pathway and its roles in NSCLC tumor microenvironment remodeling.\"},{\"question\":\"How does HGF/c-MET contribute to NSCLC tumor progression?\",\"answer\":\"It contributes to tumor cell proliferation, migration, invasion, angiogenesis, and immune evasion, acting in both normal and cancer cells.\"},{\"question\":\"What do MET-targeted therapies aim to address in NSCLC?\",\"answer\":\"MET-targeted therapies aim to counter NSCLC driven by MET alterations and to improve clinical outcomes, including in contexts such as MET exon 14 skipping or MET amplification.\"}]","Unveiling the Role of HGF/c-Met Signaling in Non-Small Cell Lung Cancer Tumor Microenvironment - read online free | PDF",1789980558,71]