[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-382195-105":59,"doc-detail-382195-en":131},{"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":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":124,"head_meta":126,"extra_data":128,"updated_unix":130},105,"en","the-roles-of-secreted-wnt-ligands-in-cancer","The Roles of Secreted Wnt Ligands in Cancer","","Wnt ligands are secreted signaling proteins with diverse biological effects, crucial for activating Wnt pathways that support tissue homeostasis and regeneration. Aberrant Wnt signaling is a cancer hallmark, arising from genetic changes that drive ligand-independent or ligand-dependent pathway hyperactivation. Recent work emphasizes Wnt-driven communication between tumor cells and the microenvironment, which can either promote or suppress tumor progression. The review details ligand functions across tumor types and links them to phenotypes such as stemness, drug resistance, metastasis, and immune evasion, and outlines strategies to target Wnt ligands therapeutically.",{"@graph":69,"@context":123},[70,84,106],{"@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":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/the-roles-of-secreted-wnt-ligands-in-cancer/382195/",{"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/the-roles-of-secreted-wnt-ligands-in-cancer/382195.png","ImageObject",300,407,{"name":92,"@type":93},"Finn","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-25","2026-09-24",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What are secreted Wnt ligands and why are they important in biology?","Question",{"text":113,"@type":114},"Wnt ligands are secreted signaling proteins that activate Wnt signaling pathways supporting tissue homeostasis and regeneration.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"How does dysregulated Wnt signaling relate to cancer?",{"text":118,"@type":114},"Dysregulation occurs through genetic alterations in Wnt components that cause ligand-independent or ligand-dependent hyperactivation of the pathway, which contributes to cancer.",{"name":120,"@type":111,"acceptedAnswer":121},"How do Wnt ligands influence tumor progression and treatment options?",{"text":122,"@type":114},"Wnt-mediated tumor–microenvironment crosstalk can promote or suppress progression and is linked to phenotypes such as stemness, drug resistance, metastasis, and immune evasion, motivating approaches to target Wnt ligands in therapy.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},382195,1790318349,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},34359740700684,"https://ap-avatar.wpscdn.com/avatar/1f400023980c374ae676?_k=1777273430885731487","Review  \nThe Roles of Secreted Wnt Ligands in Cancer  \nJohannes Werner 1,2,†, Kim E. Boonekamp 1,†, Tianzuo Zhan 3,4,5,‡ and Michael Boutros 1,5, *,‡  \nCitation: Werner, J.; Boonekamp, K.E.; Zhan, T.; Boutros, M. The Roles of Secreted Wnt Ligands in Cancer. Int. J. Mol. Sci. 2023, 24, 5349 . [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms24065349  \nAcademic Editor: Rosalba Siracusa  \nReceived: 30 January 2023  \nRevised: 28 February 2023  \nAccepted: 4 March 2023  \nPublished: 10 March 2023  \nCopyright: © 2023 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/)) .  \n1 Division of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Medical Faculty Mannheim, Heidelberg University, 69120 Heidelberg, Germany  \n2 Medical Faculty Heidelberg, Heidelberg University, 69120 Heidelberg, Germany  \n3 Department of Medicine II, Medical Faculty Mannheim, Mannheim University Hospital, Heidelberg University, D-68167 Mannheim, Germany; tianzuo.zhan@umm.de  \n4 Mannheim Cancer Center, Medical Faculty Mannheim, Heidelberg University, D-68167 Mannheim, Germany  \n5 DKFZ-Hector Cancer Institute, University Medical Center Mannheim, D-68167 Mannheim, Germany  \n* Correspondence: m.boutros@dkfz.de † These authors contributed equally to this work.  \n‡ These authors also contributed equally to this work.  \nAbstract: Wnt ligands are secreted signaling proteins that display a wide range of biological effects. They play key roles in stimulating Wnt signaling pathways to facilitate processes such as tissue homeostasis and regeneration. Dysregulation of Wnt signaling is a hallmark of many cancers and genetic alterations in various Wnt signaling components, which result in ligand-independent or ligand-dependent hyperactivation of the pathway that have been identified. Recently, research is focusing on the impact of Wnt signaling on the interaction between tumor cells and their microenvironment. This Wnt-mediated crosstalk can act either in a tumor promoting or suppressing fashion. In this review, we comprehensively outline the function of Wnt ligands in different tumor entities and their impact on key phenotypes, including cancer stemness, drug resistance, metastasis, and immune evasion. Lastly, we elaborate approaches to target Wnt ligands in cancer therapy.  \nKeywords: Wnt signaling; Wnt ligands; cancer; non-canonical Wnt signaling; tumor microenvironment; metastasis; immunotherapy; targeted therapy  \n1. Introduction  \nIn 1973, the first genomic locus of a Wnt ligand (wingless) was discovered as a crucial component for wing formation in Drosophila melanogaster [1] . In the following years, several other loci whose disruption caused segmentation defects during Drosophila development, a phenotype linked to Wnt signaling, were found to encode genes evolutionarily conserved in many other species, including vertebrates [2] . Wnt ligands (WNTs) were linked to cancer when the insertion of the mouse mammary tumor virus (MMTV) into the promoter of int1, the murine ortholog of wingless (later termed Wnt1), was discovered to induce mammary tumors in mouse models [3] . Later, it was shown in hereditary colorectal cancers that hyperactivation of the Wnt pathway is closely linked to carcinogenesis in humans [4–7] . These findings have initiated many research efforts to uncover the function of components of the Wnt pathway and its physiological roles, including WNTs, in health and disease. In this review, we provide an overview of the various roles WNTs play in tumorigenesis and tumor progression.  \n1.1. Secretion of WNTs  \nThe family of WNTs comprises 19 distinct genes in humans [8] . WNTs are cysteine-rich proteins of approximately 40 kDa si","cbCaimXCGW41eRJE","https://ap.wps.com/l/cbCaimXCGW41eRJE","pdf",2390021,27,"English","# Abstract\n# Introduction\n## Secretion of WNTs\n## The Role of Secreted WNTs in Canonical and Non-Canonical Wnt Signaling","[{\"question\":\"What are secreted Wnt ligands and why are they important in biology?\",\"answer\":\"Wnt ligands are secreted signaling proteins that activate Wnt signaling pathways supporting tissue homeostasis and regeneration.\"},{\"question\":\"How does dysregulated Wnt signaling relate to cancer?\",\"answer\":\"Dysregulation occurs through genetic alterations in Wnt components that cause ligand-independent or ligand-dependent hyperactivation of the pathway, which contributes to cancer.\"},{\"question\":\"How do Wnt ligands influence tumor progression and treatment options?\",\"answer\":\"Wnt-mediated tumor–microenvironment crosstalk can promote or suppress progression and is linked to phenotypes such as stemness, drug resistance, metastasis, and immune evasion, motivating approaches to target Wnt ligands in therapy.\"}]","The Roles of Secreted Wnt Ligands in Cancer | PDF",1790249479,68]