| First Author | Orlacchio A | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 24 | Pages | 6914-6926 |
| PubMed ID | 29055016 | Mgi Jnum | J:252305 |
| Mgi Id | MGI:6103023 | Doi | 10.1158/0008-5472.CAN-17-2105 |
| Citation | Orlacchio A, et al. (2017) SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance. Cancer Res 77(24):6914-6926 |
| abstractText | Activation of the PI3K-AKT signaling cascade is a common critical event during malignant transformation. In this study, we used thyroid gland epithelial cells and a series of genetically engineered mouse strains as model systems to demonstrate that, although necessary, AKT activation is not sufficient for PI3K-driven transformation. Instead, transformation requires the activity of the PDK1-regulated AGC family of protein kinases. In particular, SGK1 was found to be essential for proliferation and survival of thyroid cancer cells harboring PI3K-activating mutations. Notably, cotargeting SGK1 and AKT resulted in significantly higher growth suppression than inhibiting either PI3K or AKT alone. Overall, these findings underscore the clinical relevance of AKT-independent pathways in tumors driven by genetic lesions targeting the PI3K cascade. Cancer Res; 77(24); 6914-26. (c)2017 AACR. |
