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Particular attention is given to cancer-associated fibroblasts (CAFs) and how Notch-mediated stromal reprogramming can guide future TME-targeted anti-metastatic therapies.",{"@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/metastasis-and-cancer-associated-fibroblasts-taking-it-up-a-notch/337393/",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/metastasis-and-cancer-associated-fibroblasts-taking-it-up-a-notch/337393.png","ImageObject",300,407,{"name":42,"@type":43},"Logic","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-27","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",11,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why is metastasis considered difficult to study in cancer biology?","Question",{"text":63,"@type":64},"Metastasis is described as the least understood aspect of cancer biology, despite being a leading cause of cancer-related deaths.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"What role does the tumor microenvironment play in metastasis and treatment resistance?",{"text":68,"@type":64},"The TME, including stromal components and reprogrammed cells, supports tumor progression and metastasis and is linked to disease relapse and therapy resistance.",{"name":70,"@type":61,"acceptedAnswer":71},"How does Notch signaling relate to both cancer cells and the stroma?",{"text":72,"@type":64},"Notch signaling is highlighted as crucial for cancer development and progression, with recent evidence indicating involvement in the stroma and tumor microenvironment as well.","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},337393,1790727291,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,110,115,120,123,127],{"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":116,"doc_module":4,"doc_module_name":25,"category_name":117,"show_sort_weight":118,"slug":119},9,"Religion & Spirituality",20,"religion-spirituality",{"id":118,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":118,"slug":122},"World Cup","world-cup",{"id":124,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":124,"slug":126},10,"Lifestyle","lifestyle",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":97,"slug":130},19,"General","general",{"code":4,"msg":82,"data":132},{"doc_id":79,"user_id":133,"nickname":42,"user_avatar":134,"doc_module":4,"category_id":107,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":140,"language":141,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":12,"update_tm":145,"read_time":146},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","TYPE Review  \nPUBLISHED 10 January 2024 DOI 10.3389/fcell.2023.1277076  \nOPEN ACCESS  \nEDITED BY  \nBiplab Giri,  \nUniversity of Gour Banga, India  \nREVIEWED BY  \nStephen B. Keysar,  \nUniversity of Colorado Anschutz Medical  \nCampus, United States Subhash Haldar, Bose Institute, India  \n*CORRESPONDENCE  \nAnirban K. Mitra,  \n [anmitra@indiana.edu](anmitra@indiana.edu)  \nRECEIVED 14 August 2023  \nACCEPTED 27 December 2023  \nPUBLISHED 10 January 2024  \nCITATION  \nGhosh A and Mitra AK (2024), Metastasis and cancer associated fibroblasts: taking it upa NOTCH.  \nFront. Cell Dev. Biol. 11:1277076 .  \ndoi: 10.3389/fcell.2023.1277076  \nCOPYRIGHT  \n© 2024 Ghosh and Mitra. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nMetastasis and cancer associated fibroblasts: taking it up a NOTCH  \nArgha Ghosh 1,2 and Anirban K. Mitra 1,2,3*  \n1Indiana University School of Medicine-Bloomington, Bloomington, IN, United States, 2Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, IN, United States, 3Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, United States  \nMetastasis is the least understood aspect of cancer biology. 90% of cancer related deaths occur due extensive metastatic burden in patients. Apart from metastasizing cancer cells, the pro-tumorigenic and pro-metastatic role of the tumor stroma plays a crucial part in this complex process often leading to disease relapse and therapy resistance. Cellular signaling processes play a crucial role in the process of tumorigenesis and metastasis when aberrantly turned on, not just in the cancer cells, but also in the cells of the tumor microenvironment (TME) . One of the most conserved pathways includes the Notch signaling pathway that plays a crucial role in the development and progression of many cancers. In addition to its well documented role in cancer cells, recent evidence suggests crucial involvement of Notch signaling in the stroma as well. This review aims to highlight the current findings focusing on the oncogenic role of notch signaling in cancer cells and the TME, with a specific focus on cancer associated fibroblasts (CAFs), which constitute a major part of the tumor stroma and are important for tumor progression. Recent efforts have focused on the development of anti-cancer and anti-metastatic therapies targeting TME. Understanding the importance of Notch signaling in the TME would help identify important drivers for stromal reprogramming, metastasis and importantly, drive future research in the effort to develop TME-targeted therapies utilizing Notch.  \nKEYWORDS  \ncancer metastasis, tumor microenvironment, Notch signaling, cancer associated fibroblasts, ovarian cancer  \nIntroduction  \nMetastasis remains the dark matter of cancer biology. Even though it is the leading cause of cancer related deaths, we have the least understanding of this intricate process and its regulation (Lengyel, 2010; Castaneda et al., 2022; Gerstberger et al., 2023) . This is even more evident in cancers like that of the ovary, where the high metastatic burden in patients makes it the deadliest gynecological malignancy. Importantly, even though several key molecular drivers for its regulation have been identified, no current anti-metastatic therapy has been approved for the clinic. This further reduces survival expectancy of patients who have been diagnosed with metastasized tumors. Therefore, there is an urgent need to understand and unravel the complex mechanisms driving metastasis, which will help design effective therapies.  \nOver the ","cbCaie6JBIuGYP3a","https://ap.wps.com/l/cbCaie6JBIuGYP3a","pdf",1459992,21,"English","# Introduction\n## Metastasis and the tumor microenvironment\n## Notch signaling and cancer-associated fibroblasts (CAFs)\n## Therapeutic implications","[{\"question\":\"Why is metastasis considered difficult to study in cancer biology?\",\"answer\":\"Metastasis is described as the least understood aspect of cancer biology, despite being a leading cause of cancer-related deaths.\"},{\"question\":\"What role does the tumor microenvironment play in metastasis and treatment resistance?\",\"answer\":\"The TME, including stromal components and reprogrammed cells, supports tumor progression and metastasis and is linked to disease relapse and therapy resistance.\"},{\"question\":\"How does Notch signaling relate to both cancer cells and the stroma?\",\"answer\":\"Notch signaling is highlighted as crucial for cancer development and progression, with recent evidence indicating involvement in the stroma and tumor microenvironment as well.\"}]","Metastasis and cancer associated fibroblasts: taking it up a NOTCH | PDF",1790018967,53]