Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer
Abstract
:1. Introduction
2. Materials and Methods
2.1. Cell Culture and THP-1 Polarization
2.2. Co-Culture of Macrophages and CRC Cells
2.3. Cell Viability Assay
2.4. Cell Transfection and siRNA
2.5. Animal Experiments
2.6. Hematoxylin and Eosin (HE) Staining and Immunohistochemistry (IHC)
2.7. Immunofluorescence (IF)
2.8. Transcriptome Sequencing and Data Analysis
2.9. Real-Time Quantitative PCR (RT-qPCR)
2.10. Western Blot
2.11. Measurement of Lactate Production
2.12. Transwell Migration Assay
2.13. Colony Formation Assay
2.14. Statistical Analysis
3. Results
3.1. MC-LR-Promoted Malignant Progression of CRC in AOM/DSS Mice
3.2. MC-LR-Promoted Recruitment of Macrophages and M2 Macrophages’ Polarization in the TME
3.3. MC-LR-Induced IRE1α/XBP1 Pathway in CRC Cells to Promote Macrophage M2 Polarization
3.4. MC-LR-Activated IRE1α/XBP1 Signaling Pathway Promoted M2 Macrophages’ Polarization through Lactate Secretion
3.5. Inhibition of IRE1α/XBP1 Pathway and Glycolysis Suppresses MC-LR-Mediated Malignant Progression of CRC Cells in TME
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Wang, X.; Song, Y.; Lu, X.; Zhang, H.; Wang, T. Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer. Cells 2024, 13, 1439. https://doi.org/10.3390/cells13171439
Wang X, Song Y, Lu X, Zhang H, Wang T. Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer. Cells. 2024; 13(17):1439. https://doi.org/10.3390/cells13171439
Chicago/Turabian StyleWang, Xiaochang, Yuechi Song, Xiaohui Lu, Hengshuo Zhang, and Ting Wang. 2024. "Microcystin-LR Regulates Interaction between Tumor Cells and Macrophages via the IRE1α/XBP1 Signaling Pathway to Promote the Progression of Colorectal Cancer" Cells 13, no. 17: 1439. https://doi.org/10.3390/cells13171439