Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells
Abstract
:1. Introduction
2. Results
2.1. Allosteric AKT Inhibitors Preferentially Target Breast Cells Lacking CDH1
2.2. CDH1-Negative Breast Cells Have Enhanced Apoptotic Priming and Apoptosis Induction after Allosteric AKT Inhibitor Treatment
2.3. CDH1-Negative Gastric Cells Are More Sensitive to the Allosteric AKT Inhibitors ARQ-092 and MK2206
2.4. Allosteric AKT Inhibitors Preferentially Slow the Growth of Cdh1-Deleted Organoids
2.5. E-cadherin Expression Affects AKT Isoforms Differently in Breast and Gastric Cells (or in Normal and Cancer Cells)
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Small Molecule Inhibitors and Chemicals
4.3. Nuclei Enumeration Assay
4.4. Western Blotting
4.5. FACS
4.6. Apoptosis Priming
4.7. Organoid Culture
4.8. Drug Treatment of Organoids
4.9. RNA-seq Data
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Bougen-Zhukov, N.; Nouri, Y.; Godwin, T.; Taylor, M.; Hakkaart, C.; Single, A.; Brew, T.; Permina, E.; Chen, A.; Black, M.A.; et al. Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells. Cancers 2019, 11, 1359. https://doi.org/10.3390/cancers11091359
Bougen-Zhukov N, Nouri Y, Godwin T, Taylor M, Hakkaart C, Single A, Brew T, Permina E, Chen A, Black MA, et al. Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells. Cancers. 2019; 11(9):1359. https://doi.org/10.3390/cancers11091359
Chicago/Turabian StyleBougen-Zhukov, Nicola, Yasmin Nouri, Tanis Godwin, Megan Taylor, Christopher Hakkaart, Andrew Single, Tom Brew, Elizabeth Permina, Augustine Chen, Michael A. Black, and et al. 2019. "Allosteric AKT Inhibitors Target Synthetic Lethal Vulnerabilities in E-Cadherin-Deficient Cells" Cancers 11, no. 9: 1359. https://doi.org/10.3390/cancers11091359