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Updated: Jan 9, 2026
Isolation and Functional Assessment of Human Breast Cancer Stem Cells from Cell and Tissue Samples
Published on: October 2, 2020
GSK-3β Regulates Tumor Stemness and Immune-Related Pathways in Triple-Negative Breast Cancer: A Bioinformatics and
Ling Zhou1, Xinyu Wang1, Huiyin Zhu1
1Department of Thyroid and Breast Surgery, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China.
Objective:
Given the crucial roles of GSK-3β in epithelial-mesenchymal transition (EMT), we assume that it may also be involved in tumor stemness, immune evasion, and drug resistance in triple-negative breast cancer (TNBC). This study was designed to analyze the expression and clinical significance of GSK-3β and investigate its association with tumor stemness-related and immune-related genes.
Methods:
GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β-related proteins were validated via parallel reaction monitoring-based proteomics.
Results:
GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β-overexpressing cells.
Conclusion:
GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance.
