REVIEW article
Front. Oncol.
Sec. Cancer Cell Signaling
The S100 Protein Family in Bladder Cancer: Mechanisms, Clinical Value, and Targeted Therapeutic Prospects
Provisionally accepted
- 1North Sichuan Medical College, Nanchong, China
- 2Sichuan Mianyang 404 Hospital, Mianyang, China
- 3Southwest Medical University, Luzhou, China
- 4Mianyang Maternal and Child Health Hospital, Mianyang, China
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Abstract Background:Bladder cancer (BC) is a highly heterogeneous malignancy with limited molecular biomarkers and therapeutic targets. The S100 protein family, a group of calcium-binding proteins, has emerged as a crucial regulator in cancer development. However, their mechanistic roles and clinical significance in BC remain underexplored.Methods:This review summarizes the current understanding of the expression patterns, biological functions, and signaling mechanisms of key S100 family members in BC, integrating data from transcriptomic studies, public databases (The Cancer Genome Atlas Program ,Gene Expression Omnibus), and recent preclinical research.Results:S100 family members such as S100A8, S100A9, S100A13, and S100A6 are upregulated in advanced BC and are associated with tumor progression, immune suppression, and poor prognosis. In contrast, S100C exhibits tumor-suppressive properties. Mechanistically, S100 proteins promote epithelial-mesenchymal transition, angiogenesis, and immune evasion by activating receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4)-mediated signaling pathways. Emerging evidence supports the development of S100-targeted therapeutics including small molecules, monoclonal antibodies, and RAGE inhibitors. Conclusion:S100 proteins represent promising biomarkers and therapeutic targets in BC. Integrating S100-based profiling into clinical practice may improve molecular classification, prognostication, and personalized treatment. Future efforts should focus on resolving protein redundancy, validating context-specific functions, and advancing drug development for clinical translation.
Keywords: S100 protein, Bladder cancer, Immune Evasion, Rage, Epithelial-Mesenchymal Transition, biomarker, targeted therapy
Received: 11 Aug 2025; Accepted: 11 Nov 2025.
Copyright: © 2025 Zhang, Yang, Huang, Deng, Ao and Li. 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) or licensor 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.
* Correspondence: Jiabing Li, 13350961404@163.com
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