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Targeted therapies for CSCs and bulk tumors are urgent but complicated by extensive Wnt crosstalk with Hedgehog and Notch, motivating the development of Wnt inhibitors and pathway modulation to disrupt CSCs and reverse resistance mechanisms.",{"@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/wnt-signaling-pathway-in-tumor-biology-academic-article-review/337183/",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/wnt-signaling-pathway-in-tumor-biology-academic-article-review/337183.png","ImageObject",300,407,{"name":42,"@type":43},"Theodora","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-21",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",9,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why are cancer stem cells (CSCs) important in relapse and metastasis?","Question",{"text":63,"@type":64},"CSCs enable self-renewal and strong tumorigenic potential, which contributes to treatment resistance development. 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Wnt Signaling Pathway in Tumor Biology. Genes 2024, 15, 1597. [https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.3390/genes15121597](10.3390/genes15121597)  \nAcademic Editor: Stefan Hoppler  \nReceived: 30 October 2024  \nRevised: 2 December 2024  \nAccepted: 10 December 2024  \nPublished: 13 December 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/)) .  \n1 Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy,  \n400347 Cluj Napoca, Romania; [iluta.sabina@yahoo.com](iluta.sabina@yahoo.com)  \n2 Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400347 Cluj Napoca, Romania  \n3 Department of Hematology, Nicolae Testemitanu University of Medicine and Pharmacy, 2004 Chisinau, Moldova; [sanda.buruiana@usmf.md](sanda.buruiana@usmf.md)  \n4 Department of Hematology, Ion Chiricuta Oncology Institute, 400015 Cluj Napoca, Romania  \n* Correspondence: [deldima@yahoo.com](deldima@yahoo.com)  \nAbstract: Relapse and metastasis are the major challenges that stand in the way of cancer healing and survival, mainly attributed to cancer stem cells (CSCs) . Their capabilities of self-renewal and tumorigenic potential leads to treatment resistance development. CSCs function through signaling pathways such as the Wnt/β-catenin cascade. While commonly involved in embryogenesis and adult tissues homeostasis, the dysregulation of the Wnt pathway has direct correlations with tumorigenesis, metastasis, and drug resistance. The development of therapies that target CSCs and bulk tumors is both crucial and urgent. However, the extensive crosstalk present between Wnt and other signaling networks (Hedgehog and Notch) complicates the development of efficient long-term therapies with minimal side-effects on normal tissues. Despite the obstacles, the emergence of Wnt inhibitors and subsequent modulation of the signaling pathways would provide dynamic therapeutic approaches to impairing CSCs and reversing resistance mechanisms.  \nKeywords: Wnt pathway; cancer stem cells; tumor biology  \n1. Introduction  \nWnt, Notch, and Hedgehog (Hh) are developmental signaling pathway with vital importance in regulating cell fate decisions like tissue growth and homeostasis or stem cell renewal, migration, or differentiation [1] . These processes are indispensable for tissues like blood, brain, skin, lungs, and intestine. However, with such fundamental implications in basic cellular processes, these signaling networks are often prone to malfunctioning into human malignancies. The ongoing study of cancer has brought important observations such as the constant presence in tumors of a subpopulation of cells with stem-like properties, notoriously known as cancer stem cells (CSCs) [2] .  \nVarious key signaling networks, mainly Hh, Notch, and Wnt, appear to influence the fate and behavior of CSCs. This, indeed, presents both challenges and opportunities, as targeted antagonization of such pathways may give rise to promising anti-cancer treatments. In the last decade, CSCs were recognized in various cancers. The presence of tumor heterogeneity and small populations of cells with stem-like properties have been established in the majority of malignancies, although debates about their origins and plasticity continue [3] .  \nThese CSCs share a number of similarities with embryonic or tissue stem cells and are often characterized by the sustained activation of well-conserved signaling pathways such as Notch, Hh, and Wnt. In additi","cbCaivUjT6ALOyBi","https://ap.wps.com/l/cbCaivUjT6ALOyBi","pdf",281533,13,"English","# Introduction\n## Wnt/β-catenin Signaling, Embryogenesis, Cell Cycle Regulation, and Cancer Development","[{\"question\":\"Why are cancer stem cells (CSCs) important in relapse and metastasis?\",\"answer\":\"CSCs enable self-renewal and strong tumorigenic potential, which contributes to treatment resistance development. Their behavior supports ongoing disease progression, including relapse and metastasis.\"},{\"question\":\"How does dysregulation of the Wnt pathway relate to cancer progression?\",\"answer\":\"The Wnt pathway is connected to tumorigenesis, metastasis, and drug resistance when its regulation is disrupted. Wnt signaling activity influences cancer development and CSC function.\"},{\"question\":\"What makes developing long-term therapies targeting Wnt challenging?\",\"answer\":\"Wnt signaling extensively crosstalks with other pathways such as Hedgehog and Notch. This interconnection complicates designing efficient long-term treatments with minimal effects on normal tissues.\"}]","Wnt Signaling Pathway in Tumor Biology - Academic Article Review | PDF",1790018043,33]