SGK1 is a critical component of an AKT-independent pathway essential for PI3K-mediated tumor development and maintenance

Arturo Orlacchio, Michela Ranieri, Martina Brave, Valeria Antico Arciuch, Toni Forde, Daniela De Martino, Karen E. Anderson, Phillip Hawkins, Antonio Di Cristofano

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6914-6926
Number of pages13
JournalCancer research
Volume77
Issue number24
DOIs
StatePublished - Dec 15 2017

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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