Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications

Abstract The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contribu...

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Main Authors: Trang Thao Quoc Pham, Yung-Che Kuo, Wei-Ling Chang, Hao-Jui Weng, Yen-Hua Huang
Format: Article
Language:English
Published: BMC 2025-05-01
Series:Molecular Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12943-025-02289-8
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author Trang Thao Quoc Pham
Yung-Che Kuo
Wei-Ling Chang
Hao-Jui Weng
Yen-Hua Huang
author_facet Trang Thao Quoc Pham
Yung-Che Kuo
Wei-Ling Chang
Hao-Jui Weng
Yen-Hua Huang
author_sort Trang Thao Quoc Pham
collection DOAJ
description Abstract The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.
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institution OA Journals
issn 1476-4598
language English
publishDate 2025-05-01
publisher BMC
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series Molecular Cancer
spelling doaj-art-118a5c3a04b5414f980e6a4c2d94f0622025-08-20T01:52:26ZengBMCMolecular Cancer1476-45982025-05-0124116110.1186/s12943-025-02289-8Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applicationsTrang Thao Quoc Pham0Yung-Che Kuo1Wei-Ling Chang2Hao-Jui Weng3Yen-Hua Huang4International Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical UniversityTMU Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical UniversityInternational Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical UniversityInternational Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical UniversityInternational Ph.D. Program in Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical UniversityAbstract The niche microenvironment plays a crucial role in regulating the fate of normal skin stem cells (SSCs) and cancer stem cells (CSCs). Therapeutically targeting the CSC niche holds promise as an effective strategy; however, the dual effects of shared SSC niche signaling in CSCs have contributed to the aggressive characteristics of tumors and poor survival rates in skin cancer patients. The lack of a clear underlying mechanism has significantly hindered drug development for effective treatment. This article explores recent advances in understanding how niche factors regulate cell fate determination between skin stem cells and skin CSCs, along with their clinical implications. The dual roles of key components of the adhesive niche, including the dermo-epidermal junction and adherens junction, various cell types—especially immune cells and fibroblasts—as well as major signaling pathways such as Sonic hedgehog (Shh), Wingless-related integration site (Wnt)/β-catenin, YAP (Yes-associated protein)/TAZ (transcriptional coactivator with PDZ-binding motif), and Notch, are highlighted. Additionally, recent advances in clinical trials and drug development targeting these pathways are discussed. Overall, this review provides valuable insights into the complex interactions between skin cancer stem cells and their microenvironment, laying the groundwork for future research and clinical strategies.https://doi.org/10.1186/s12943-025-02289-8Niche regulationSkin stem cellCancer stem cellDrug resistanceShh/Wnt/YAP/Notch signalingTherapeutic targeting
spellingShingle Trang Thao Quoc Pham
Yung-Che Kuo
Wei-Ling Chang
Hao-Jui Weng
Yen-Hua Huang
Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
Molecular Cancer
Niche regulation
Skin stem cell
Cancer stem cell
Drug resistance
Shh/Wnt/YAP/Notch signaling
Therapeutic targeting
title Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
title_full Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
title_fullStr Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
title_full_unstemmed Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
title_short Double-sided niche regulation in skin stem cell and cancer: mechanisms and clinical applications
title_sort double sided niche regulation in skin stem cell and cancer mechanisms and clinical applications
topic Niche regulation
Skin stem cell
Cancer stem cell
Drug resistance
Shh/Wnt/YAP/Notch signaling
Therapeutic targeting
url https://doi.org/10.1186/s12943-025-02289-8
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AT yungchekuo doublesidednicheregulationinskinstemcellandcancermechanismsandclinicalapplications
AT weilingchang doublesidednicheregulationinskinstemcellandcancermechanismsandclinicalapplications
AT haojuiweng doublesidednicheregulationinskinstemcellandcancermechanismsandclinicalapplications
AT yenhuahuang doublesidednicheregulationinskinstemcellandcancermechanismsandclinicalapplications