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 journalArticle

6 Citations (Scopus)

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

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Phosphatidylinositol 3-Kinases
Maintenance
Neoplasms
Thyroid Neoplasms
Protein Kinases
Thyroid Gland
Mutation
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

SGK1 is a critical component of an AKT-independent pathway essential for PI3K-mediated tumor development and maintenance. / Orlacchio, Arturo; Ranieri, Michela; Brave, Martina; Arciuch, Valeria Antico; Forde, Toni; De Martino, Daniela; Anderson, Karen E.; Hawkins, Phillip; Di Cristofano, Antonio.

In: Cancer Research, Vol. 77, No. 24, 15.12.2017, p. 6914-6926.

Research output: Contribution to journalArticle

Orlacchio, A, Ranieri, M, Brave, M, Arciuch, VA, Forde, T, De Martino, D, Anderson, KE, Hawkins, P & Di Cristofano, A 2017, 'SGK1 is a critical component of an AKT-independent pathway essential for PI3K-mediated tumor development and maintenance', Cancer Research, vol. 77, no. 24, pp. 6914-6926. https://doi.org/10.1158/0008-5472.CAN-17-2105
Orlacchio, Arturo ; Ranieri, Michela ; Brave, Martina ; Arciuch, Valeria Antico ; Forde, Toni ; De Martino, Daniela ; Anderson, Karen E. ; Hawkins, Phillip ; Di Cristofano, Antonio. / SGK1 is a critical component of an AKT-independent pathway essential for PI3K-mediated tumor development and maintenance. In: Cancer Research. 2017 ; Vol. 77, No. 24. pp. 6914-6926.
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