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SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance.

SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance.
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Orlacchio A, Ranieri M, Brave M, Arciuch VA, Forde T, De Martino D, Anderson KE, Hawkins P, Di Cristofano A,


Orlacchio A, Ranieri M, Brave M, Arciuch VA, Forde T, De Martino D, Anderson KE, Hawkins P, Di Cristofano A, (click to view)

Orlacchio A, Ranieri M, Brave M, Arciuch VA, Forde T, De Martino D, Anderson KE, Hawkins P, Di Cristofano A,

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Cancer research 2017 10 2077(24) 6914-6926 doi 10.1158/0008-5472.CAN-17-2105

Abstract

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. ©2017 AACR.

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