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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| Format: | Article |
| Language: | English |
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BMC
2025-05-01
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| Series: | Molecular Cancer |
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| 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. |
| format | Article |
| id | doaj-art-118a5c3a04b5414f980e6a4c2d94f062 |
| institution | OA Journals |
| issn | 1476-4598 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| 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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