Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. Mutation in KRAS Gene Diminishes the Antiproliferative Effect of Cetuximab in CRC Cells
2.2. 5-FU Induces YB-1 Phosphorylation at S102 in KRAS(G13D)-Mutated HCT116 Cells but Not in KRAS Wild-Type SW48 Cells
2.3. Targeting RSK by LJI308 Inhibits Phosphorylation of YB-1 at S102 in CRC Cells
2.4. Upregulation of Akt after RSK Targeting Interferes with the Antiproliferative Effect of the LJI308 RSK Inhibitor
2.5. Dual Targeting of the RSK/YB-1 Pathway and Akt Enhances the Antiproliferative Effect of 5-FU in KRAS(G13D)-Mutated HCT116 Cells but Not in KRAS Wild-Type SW48 Cells by Stimulating Apoptosis
2.6. Dual Targeting of the RSK/YB-1 Pathway and Akt Enhances the Clonogenic Inactivation by 5-FU in KRAS(G13D)-Mutated HCT116 Cells
2.7. YB-1 Is Highly Phosphorylated in CRC Patient Tumor Tissues
3. Discussion
4. Materials and Methods
4.1. Cell Lines
4.2. Antibodies and Reagents
4.3. Western Blotting
4.4. Proliferation Assay
4.5. Cell Cycle Analysis
4.6. Human Phospho-MAPK Array
4.7. Clonogenic Assay
4.8. Transfection with siRNA
4.9. Immunofluorescence Analysis
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Maier, E.; Attenberger, F.; Tiwari, A.; Lettau, K.; Rebholz, S.; Fehrenbacher, B.; Schaller, M.; Gani, C.; Toulany, M. Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells. Cancers 2019, 11, 562. https://doi.org/10.3390/cancers11040562
Maier E, Attenberger F, Tiwari A, Lettau K, Rebholz S, Fehrenbacher B, Schaller M, Gani C, Toulany M. Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells. Cancers. 2019; 11(4):562. https://doi.org/10.3390/cancers11040562
Chicago/Turabian StyleMaier, Eva, Felix Attenberger, Aadhya Tiwari, Konstanze Lettau, Simone Rebholz, Birgit Fehrenbacher, Martin Schaller, Cihan Gani, and Mahmoud Toulany. 2019. "Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells" Cancers 11, no. 4: 562. https://doi.org/10.3390/cancers11040562
APA StyleMaier, E., Attenberger, F., Tiwari, A., Lettau, K., Rebholz, S., Fehrenbacher, B., Schaller, M., Gani, C., & Toulany, M. (2019). Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells. Cancers, 11(4), 562. https://doi.org/10.3390/cancers11040562