[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-364780-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-364780-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","survival-strategies-of-cancer-cells-the-role-of-macropinocytosis-in-nutrient-acquisition-metabolic-reprogramming-and-therapeutic-targeting","Survival strategies of cancer cells - the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting","","Macropinocytosis is a nonselective endocytic process that enables cancer cells to take up extracellular fluid and its contents, including nutrients and growth factors. The review details macropinocytosis step by step and emphasizes the central regulatory role of the MTOR complex 1 (MTORC1) as a signaling hub coordinating nutrient uptake and metabolic programs. It synthesizes molecular evidence on initiation, maturation, and recycling of macropinosomes, highlighting how cancers hijack these events to sustain growth. The article discusses therapeutic targeting options, including improved drug delivery, starvation by inhibition, blocking degradation/recycling, and methuosis, a cell death driven by excessive macropinocytosis. Such targeting may advance therapies for cancers dependent on this pathway.",{"@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/survival-strategies-of-cancer-cells-the-role-of-macropinocytosis-in-nutrient-acquisition-metabolic-reprogramming-and-therapeutic-targeting/364780/",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/survival-strategies-of-cancer-cells-the-role-of-macropinocytosis-in-nutrient-acquisition-metabolic-reprogramming-and-therapeutic-targeting/364780.png","ImageObject",300,407,{"name":42,"@type":43},"Miles","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",8,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"What is macropinocytosis and why is it important for cancer cells?","Question",{"text":63,"@type":64},"Macropinocytosis is a nonselective endocytosis route that engulfs extracellular fluid and its dissolved contents. Cancer cells use it to acquire nutrients and growth factors that support survival and growth.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How does MTORC1 influence macropinocytosis and metabolic reprogramming?",{"text":68,"@type":64},"MTORC1 functions as a key signaling hub that integrates pathways controlling nutrient uptake and metabolic processes. The review highlights its central role in regulating macropinocytosis.",{"name":70,"@type":61,"acceptedAnswer":71},"Which therapeutic strategies targeting macropinocytosis are discussed?",{"text":72,"@type":64},"The review discusses strategies such as enhancing drug delivery via macropinocytosis, inhibiting the process to deprive cancer cells of resources, blocking macropinosome degradation and recycling, and inducing methuosis through excessive macropinocytosis.","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},364780,1790470601,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,114,119,122,126],{"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":55,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"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":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":145},13056703019404,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","AUTOPHAGY  \n2025, VOL. 21, NO. 4, 693–718  \n[https://doi.org/10.1080/15548627.2025.2452149](https://doi.org/10.1080/15548627.2025.2452149)  \nREVIEW  \nSurvival strategies of cancer cells: the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting  \nGuoshuai Xu a, Qinghong Zhangb, Renjia Chengc, Jun Qua, and Wenqiang Li a  \naDepartment of General Surgery, Aerospace Center Hospital, Beijing, China; bEmergency Department, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China; cDepartment of Intensive Care Medicine, The General Hospital of the Northern Theater Command of the People’s Liberation Army of China, Shenyang, Liaoning, China  \nABSTRACT  \nMacropinocytosis is a nonselective form of endocytosis that allows cancer cells to largely take up the extracellular fluid and its contents, including nutrients, growth factors, etc. We first elaborate meticulously on the process of macropinocytosis. Only by thoroughly understanding this entire process can we devise targeted strategies against it. We then focus on the central role of the MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) in regulating macropinocytosis, highlighting its significance as a key signaling hub where various pathways converge to control nutrient uptake and metabolic processes. The article covers a comprehensive analysis of the literature on the molecular mechanisms governing macropinocytosis, including the initiation, maturation, and recycling of macropinosomes, with an emphasis on how these processes are hijacked by cancer cells to sustain their growth. Key discussions include the potential therapeutic strategies targeting macropinocytosis, such as enhancing drug delivery via this pathway, inhibiting macropinocytosis to starve cancer cells, blocking the degradation and recycling of macropinosomes, and inducing methuosis – a form of cell death triggered by excessive macropinocytosis. Targeting macropinocytosis represents a novel and innovative approach that could significantly advance the treatment of cancers that rely on this pathway for survival. Through continuous research and innovation, we look forward to developing more effective and safer anti-cancer therapies that will bring new hope to patients.  \nAbbreviation: AMPK: AMP-activated protein kinase; ASOs: antisense oligonucleotides; CAD: carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase; DC: dendritic cell; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; ERBB2: erb-b2 receptor tyrosine kinase 2; ESCRT: endosomal sorting complex required for transport; GAP: GTPaseactivating protein; GEF: guanine nucleotide exchange factor; GRB2: growth factor receptor bound protein 2; LPP: lipopolyplex; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; MTORC2: mechanistic target of rapamycin kinase complex 2; NSCLC: non-small cell lung cancer; PADC: pancreatic ductal adenocarcinoma; PDPK1: 3-phosphoinositide dependent protein kinase 1; PI3K: phosphoinositide 3-kinase; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PtdIns(3,4,5)P3: phosphatidylinositol-(3,4,5)-trisphosphate; PtdIns(4,5)P2: phosphatidylinositol-(4,5)-bisphosphate; PTT: photothermal therapies; RAC1: Rac family small GTPase 1; RPS6: ribosomal protein S6; RPS6KB1: ribosomal protein S6 kinase B1; RTKs: receptor tyrosine kinases; SREBF: sterol regulatory element binding transcription factor; TFEB: transcription factor EB; TNBC: triple-negative breast cancer; TSC2: TSC complex subunit 2; ULK1: unc-51 like autophagy activating kinase 1; UPS: ubiquitin-proteasome system.  \nARTICLE HISTORY  \nReceived 9 October 2024 Revised 27 December 2024 Accepted 7 January 2025  \nKEYWORDS  \nAnti-cancer therapies; macropinocytosis; metabolic reprogramming; methuosis; MTORC1; MTORC2  \nIntroduction  \nEndocytosis is a fundamental cellular process by which cells internalize extracellular","cbCaisfnAENAuuGx","https://ap.wps.com/l/cbCaisfnAENAuuGx","pdf",1939902,26,"English","# Introduction\n## Endocytosis mechanisms and relevance to cancer\n# Abstract and scope of the review\n## Macropinocytosis process\n## MTORC1 as a regulatory hub\n## Molecular mechanisms: initiation, maturation, recycling\n## Cancer hijacking of macropinocytosis\n## Therapeutic targeting strategies","[{\"question\":\"What is macropinocytosis and why is it important for cancer cells?\",\"answer\":\"Macropinocytosis is a nonselective endocytosis route that engulfs extracellular fluid and its dissolved contents. Cancer cells use it to acquire nutrients and growth factors that support survival and growth.\"},{\"question\":\"How does MTORC1 influence macropinocytosis and metabolic reprogramming?\",\"answer\":\"MTORC1 functions as a key signaling hub that integrates pathways controlling nutrient uptake and metabolic processes. The review highlights its central role in regulating macropinocytosis.\"},{\"question\":\"Which therapeutic strategies targeting macropinocytosis are discussed?\",\"answer\":\"The review discusses strategies such as enhancing drug delivery via macropinocytosis, inhibiting the process to deprive cancer cells of resources, blocking macropinosome degradation and recycling, and inducing methuosis through excessive macropinocytosis.\"}]","Survival strategies of cancer cells - the role of macropinocytosis in nutrient acquisition, metabolic reprogramming, and therapeutic targeting | PDF",1790159023,66]