[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-detail-405514-en":59,"doc-seo-405514-105":80},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":5,"data":60},{"doc_id":61,"user_id":62,"nickname":63,"user_avatar":64,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":66,"doc_content":67,"file_id":68,"file_url":69,"file_type":70,"file_size":71,"view_count":44,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":24,"language":72,"language_code":73,"site_id":74,"html_lang":73,"table_of_contents":75,"faqs":76,"seo_title":77,"seo_description":66,"update_tm":78,"read_time":79,"preview_page_count":4},405514,3848291630094,"Emma Wilson","https://eur-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","EGFR endocytosis: more than meets the eye","EGFR endocytosis controls the intracellular destiny of proteins initiated by activated receptors, directing internalized components either to lysosomal degradation or to recycling back to the cell surface or trans-Golgi network. Progress in endocytic mechanism research highlights how deregulated endocytic pathways contribute to disease, particularly cancer. This review focuses on the EGF-SNX3-EGFR axis in breast cancers, extending discussion to canonical and non-canonical roles of endocytic proteins in EGFR endocytosis within cancer.","[www.oncotarget.com](www.oncotarget.com) Oncotarget, 2023, Vol. 14, pp: 297-301  \nEditorial Perspective  \nEGFR endocytosis: more than meets the eye  \nAysegul Sapmaz and Ayse Elif Erson-Bensan  \nABSTRACT  \nBehind the scenes of signaling cascades initiated by activated receptors, endocytosis determines the fate of internalized proteins through degradation in lysosomes or recycling. Over the years, significant progress has been made in understanding the mechanisms of endocytosis and deregulation in disease states. Here we review the role of the EGF-SNX3-EGFR axis in breast cancers with an extended discussion on deregulated EGFR endocytosis in cancer.  \nINTRODUCTION  \nEGFR (Epidermal growth factor receptor) and other cell-surface receptors (e.g., junctional proteins, growth factor receptors, and integrins) have pivotal roles during development and tumorigenesis [1] . Behind the scenes of signaling cascades initiated by activated receptors, endocytosis determines the fate of internalized proteins through degradation in lysosomes or recycling them back to the cell surface or trans-Golgi network (TGN) . Over the years, significant progress has improved the understanding of the mechanisms of endocytosis.  \nDifferent types of endocytosis (i.e., receptormediated endocytosis, clathrin-dependent and-independent endocytosis, caveolar pathway) are generally viewed as away of receptor attenuation. In contrast, endocytosis also sustains the signaling cascades. Moreover, the roles of endocytic processes in diverse physiological functions, including autophagy, apoptosis, cellular defense, and immune responses, are gaining attention [2, 3] . Hence, endocytic processes may also become oncogenic when deregulated during tumorigenesis, metastasis, and drug resistance in cancers [4] . Here we review the role of the EGF-SNX3-EGFR axis in breast cancers with an extended discussion on canonical and non-canonical functions of endocytic proteins involved in EGFR endocytosis in cancer.  \nEGFR ENDOCYTOSIS IN CANCER  \nHigh expression of EGFR and its activating mutations in specific cancer types are linked to diverse malignant phenotypes, including stemness, invasion, metastasis, and drug resistance. The underlying mechanisms of EGFR upregulation and oncogenic activity include mutations, amplification of the EGFR gene locus, and defective endocytosis.  \nTypically, activated and phosphorylated EGFRs undergo internalization and trafficking from the early  \nendosomes to the late endosomes and the lysosomes for degradation. Alternatively, internalized EGFRs are recycled back to the plasma membrane. These processes are heavily dependent on post-translational modifications (e.g., ubiquitination) and are regulated by multiple proteins, including adaptors (e.g., EPS15, Hrs, and STAM), small Rab GTPases, and sorting nexin proteins [5] . Hence deregulation of these players in endocytic processes has significant implications for EGFR activity in cancers.  \nUbiquitination  \nUbiquitin serves as a sorting signal during the endocytosis of EGFR while also regulating endocytic proteins [6] . Ligand-activated and autophosphorylated EGFR binds to the E3 ubiquitin ligase, CBL (Casitas B-lineage lymphoma), and gets ubiquitinated, which is essential for clathrin-independent endocytosis (CIE) of EGFR internalization upon high EGF concentrations. CBL directly binds to Py1045 or indirectly via GRB2 adaptor protein to pY1068/pY1086 residues of EGFR. Consequently, EGFR enters the degradation route to the lysosome to prevent continuous receptor activation (reviewed in [7]) . In contrast, in cancers, loss of function mutants ofCBL have oncogenic activity by enhancing a prolonged receptor tyrosine kinase signaling [8–10] .  \nUbiquitination ofEGFR is also critical for recruiting the adaptor protein, Epidermal Growth Factor Pathway Substrate 15 (EPS15), to coated pits, which is also an essential step for the internalization of EGFR into early endosomes. To get degraded in the lysosome, ubiq","cbCaijLcIJbCIiDS","https://ap.wps.com/l/cbCaijLcIJbCIiDS","pdf",448846,"English","en",105,"# Editorial Perspective\n## EGFR endocytosis: more than meets the eye\n## Abstract\n## Introduction\n## EGFR endocytosis in cancer\n## Ubiquitination\n## Small Rab GTPases","[{\"question\":\"What role does endocytosis play in receptor signaling outcomes?\",\"answer\":\"Endocytosis determines the fate of internalized proteins by directing them toward lysosomal degradation or recycling back to the cell surface or the trans-Golgi network.\"},{\"question\":\"How do deregulations in EGFR endocytosis contribute to cancer?\",\"answer\":\"Defective endocytosis and deregulated endocytic proteins can sustain or prolong oncogenic EGFR activity, promoting malignant phenotypes such as stemness, invasion, metastasis, and drug resistance.\"},{\"question\":\"Why is EGFR ubiquitination important for receptor attenuation?\",\"answer\":\"Ubiquitination acts as a sorting signal that supports internalization routing toward lysosomal degradation, preventing continuous receptor activation; loss of proper ubiquitination can allow escape from signal attenuation in cancer cells.\"}]","EGFR endocytosis: more than meets the eye | PDF",1790560331,13,{"code":4,"msg":81,"data":82},"ok",{"site_id":74,"language":73,"slug":83,"title":65,"keywords":84,"description":66,"schema_data":85,"social_meta":139,"head_meta":141,"extra_data":143,"updated_unix":144},"egfr-endocytosis-more-than-meets-the-eye","",{"@graph":86,"@context":138},[87,101,121],{"@type":88,"itemListElement":89},"BreadcrumbList",[90,94,96,99],{"item":91,"name":92,"@type":93,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":95,"name":9,"@type":93,"position":14},"https://docshare.wps.com/document/",{"item":97,"name":35,"@type":93,"position":98},"https://docshare.wps.com/document/healthcare/",3,{"item":100,"name":65,"@type":93,"position":19},"https://docshare.wps.com/document/egfr-endocytosis-more-than-meets-the-eye/405514/",{"url":100,"name":65,"@type":102,"image":103,"author":108,"headline":65,"publisher":110,"fileFormat":113,"inLanguage":73,"description":66,"dateModified":114,"datePublished":115,"encodingFormat":113,"isAccessibleForFree":116,"interactionStatistic":117},"DigitalDocument",{"url":104,"@type":105,"width":106,"height":107},"https://docshare.wps.com/thumbnails/egfr-endocytosis-more-than-meets-the-eye/405514.png","ImageObject",300,407,{"name":63,"@type":109},"Person",{"url":91,"name":111,"@type":112},"DocShare","Organization","application/pdf","2026-10-31","2026-09-28",true,{"@type":118,"interactionType":119,"userInteractionCount":44},"InteractionCounter",{"@type":120},"ViewAction",{"@type":122,"mainEntity":123},"FAQPage",[124,130,134],{"name":125,"@type":126,"acceptedAnswer":127},"What role does endocytosis play in receptor signaling outcomes?","Question",{"text":128,"@type":129},"Endocytosis determines the fate of internalized proteins by directing them toward lysosomal degradation or recycling back to the cell surface or the trans-Golgi network.","Answer",{"name":131,"@type":126,"acceptedAnswer":132},"How do deregulations in EGFR endocytosis contribute to cancer?",{"text":133,"@type":129},"Defective endocytosis and deregulated endocytic proteins can sustain or prolong oncogenic EGFR activity, promoting malignant phenotypes such as stemness, invasion, metastasis, and drug resistance.",{"name":135,"@type":126,"acceptedAnswer":136},"Why is EGFR ubiquitination important for receptor attenuation?",{"text":137,"@type":129},"Ubiquitination acts as a sorting signal that supports internalization routing toward lysosomal degradation, preventing continuous receptor activation; loss of proper ubiquitination can allow escape from signal attenuation in cancer cells.","https://schema.org",{"og:url":100,"og:type":140,"og:title":65,"og:site_name":111,"og:description":66},"article",{"robots":142,"canonical":100},"index,follow",{"doc_id":61,"site_id":74},1791263132]