Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Methods
2.1. Cell Culture
2.2. Drugs
2.3. In Vivo Studies
2.4. Protein Collection and Western Blots
2.5. RNA Isolation and RNA-seq
2.6. Real-Time Quantitative RT-PCR
2.7. Patient Tumor Samples
2.8. Immunohistochemistry and Scoring
2.9. Cell Growth Assays
2.10. Bioinformatics
2.11. Statistical Methods
3. Results
3.1. Inhibition of mTORC1 Signaling in Resistant Tumors Modulates the Expression of Extracellular Matrix Genes
3.2. The Extracellular Matrix and FAK Activation Are Associated with Resistance to mTORC1 Inhibitors
3.3. FAK Activation Is Associated with Poor Breast Cancer Patient Outcomes
3.4. Pharmacologically Inhibiting mTORC1 Activity Increases the Expression of a FAK Signature Gene Set
3.5. FAK Blockade Conveys Sensitivity to mTORC1 Inhibition in Resistant/Moderately Resistant Tumors
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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Cuellar-Vite, L.; Weber-Bonk, K.L.; Abdul-Karim, F.W.; Booth, C.N.; Keri, R.A. Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy. Cancers 2022, 14, 3374. https://doi.org/10.3390/cancers14143374
Cuellar-Vite L, Weber-Bonk KL, Abdul-Karim FW, Booth CN, Keri RA. Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy. Cancers. 2022; 14(14):3374. https://doi.org/10.3390/cancers14143374
Chicago/Turabian StyleCuellar-Vite, Leslie, Kristen L. Weber-Bonk, Fadi W. Abdul-Karim, Christine N. Booth, and Ruth A. Keri. 2022. "Focal Adhesion Kinase Provides a Collateral Vulnerability That Can Be Leveraged to Improve mTORC1 Inhibitor Efficacy" Cancers 14, no. 14: 3374. https://doi.org/10.3390/cancers14143374