A Tumor Microenvironment-Driven Network Regulated by STAT3 and p65 Negatively Controls the Enrichment of Cancer Stem Cells in Human HR+/HER2− Breast Cancer
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Cell Cultures
2.2. Cell Exposure to TME Stimulation
2.3. Flow Cytometry Analyses
2.4. ELISA Analyses
2.5. Transcriptome RNAseq Analyses
2.6. Western Blot Analyses
2.7. Knock-Down of Target Genes
2.8. Generation of Cells Over-Expressing Wild Type STAT3 or Mutant STAT3
2.9. Analyses of Patient Databases
2.10. Data Presentation and Statistical Analyses
3. Results
3.1. TME Stimulation Promotes Multiple Tumor-Supporting Characteristics and Functions in HR+/HER2− Breast Cancer Cells
3.2. TME Stimulation Leads to Pronounced Alterations in Gene Signatures of HR+/HER2− Breast Cancer Cells
3.3. STAT3 Regulates the Pro-Metastatic Activities of TME-Stimulated HR+/HER2− Breast Cancer Cells
3.4. When the Entire STAT3 Protein Is Absent, Its Regulatory Effects Are Compensated by p65 Activation
3.5. The Negative Regulatory Roles of Y705-STAT3 + p65 on CSC Enrichment Have Clinical Relevance
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Ben-Yaakov, H.; Meshel, T.; Pasmanik-Chor, M.; Körner, C.; Ben-Baruch, A. A Tumor Microenvironment-Driven Network Regulated by STAT3 and p65 Negatively Controls the Enrichment of Cancer Stem Cells in Human HR+/HER2− Breast Cancer. Cancers 2023, 15, 2255. https://doi.org/10.3390/cancers15082255
Ben-Yaakov H, Meshel T, Pasmanik-Chor M, Körner C, Ben-Baruch A. A Tumor Microenvironment-Driven Network Regulated by STAT3 and p65 Negatively Controls the Enrichment of Cancer Stem Cells in Human HR+/HER2− Breast Cancer. Cancers. 2023; 15(8):2255. https://doi.org/10.3390/cancers15082255
Chicago/Turabian StyleBen-Yaakov, Hagar, Tsipi Meshel, Metsada Pasmanik-Chor, Cindy Körner, and Adit Ben-Baruch. 2023. "A Tumor Microenvironment-Driven Network Regulated by STAT3 and p65 Negatively Controls the Enrichment of Cancer Stem Cells in Human HR+/HER2− Breast Cancer" Cancers 15, no. 8: 2255. https://doi.org/10.3390/cancers15082255