SGK1 in Cancer: Biomarker and Drug Target
Jonas Cicenas, Edita Meškinytė-Kaušilienė, Vigilijus Jukna, Arnas Rimkus, Jokubas Simkus, Diana Soderholm
Abstract
Serum- and glucocorticoid-regulated kinases (SGKs) are members of the AGC family of serine/threonine kinases, consisting of three isoforms: SGK1, SGK2, and SGK3. SGK1 was initially cloned as a gene transcriptionally stimulated by serum and glucocorticoids in rat mammary tumor cells. It is upregulated in some cancers and downregulated in others. SGK1 increases tumor cell survival, adhesiveness, invasiveness, motility, and epithelial to mesenchymal transition. It stimulates tumor growth by mechanisms such as activation of K+ channels and Ca2+ channels, Na+/H+ exchanger, amino acid and glucose transporters, downregulation of Foxo3a and p53, and upregulation of β-catenin and NFκB. This chapter focuses on major aspects of SGK1 involvement in cancer, its use as biomarker as well as potential therapeutic target.