American Association for Cancer Research
00085472can172105-sup-186301_2_supp_4331594_3xtlfm.pdf (264.28 kB)

Figure S5 from SGK1 Is a Critical Component of an AKT-Independent Pathway Essential for PI3K-Mediated Tumor Development and Maintenance

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journal contribution
posted on 2023-03-31, 00:42 authored by Arturo Orlacchio, Michela Ranieri, Martina Brave, Valeria Antico Arciuch, Toni Forde, Daniela De Martino, Karen E. Anderson, Phillip Hawkins, Antonio Di Cristofano

Combined pharmacological targeting of PI3K and SGKs at a constant inhibitors ratio does not result in synergistic activity.


Albert Einstein Cancer Center




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.