1. SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition.
- Author
-
Talarico C, Dattilo V, D'Antona L, Menniti M, Bianco C, Ortuso F, Alcaro S, Schenone S, Perrotti N, and Amato R
- Subjects
- Animals, Caspases genetics, Caspases metabolism, Cell Cycle Proteins genetics, Cell Cycle Proteins metabolism, Drug Resistance, Neoplasm genetics, Humans, Immediate-Early Proteins antagonists & inhibitors, Immediate-Early Proteins metabolism, Isoenzymes genetics, Isoenzymes metabolism, Neoplasm Proteins antagonists & inhibitors, Neoplasm Proteins metabolism, Neoplasms genetics, Neoplasms metabolism, Neoplasms pathology, Oxidative Stress, Protein Serine-Threonine Kinases antagonists & inhibitors, Protein Serine-Threonine Kinases metabolism, Radiation Tolerance genetics, Signal Transduction, Transcription Factors genetics, Transcription Factors metabolism, Antineoplastic Agents therapeutic use, Gamma Rays therapeutic use, Gene Expression Regulation, Neoplastic, Immediate-Early Proteins genetics, Neoplasm Proteins genetics, Neoplasms therapy, Protein Serine-Threonine Kinases genetics
- Abstract
The serum- and glucocorticoid-regulated kinase (SGK) family consists of three members, SGK1, SGK2 and SGK3, all displaying serine/threonine kinase activity and sharing structural and functional similarities with the AKT family of kinases. SGK1 was originally described as a key enzyme in the hormonal regulation of several ion channels and pumps. Over time, growing and impressive evidence has been accumulated, linking SGK1 to the cell survival, de-differentiation, cell cycle control, regulation of caspases, response to chemical, mechanical and oxidative injury in cancer models as well as to the control of mitotic stability. Much evidence shows that SGK1 is over-expressed in a variety of epithelial tumors. More recently, many contributions to the published literature demonstrate that SGK1 can mediate chemo-and radio-resistance during the treatment of various human tumors, both in vitro and in vivo. SGK1 appears therefore as a dirty player in the stress response to chemical and radio-agents, responsible of a selective advantage that favors the uncontrolled tumor progression and the selection of the most aggressive clones. The purpose of this review is the analysis of the literature describing SGK1 as central node of the cell resistance, and a summary of the possible strategies in the pharmacological targeting of SGK1., (© 2016 The Author(s) Published by S. Karger AG, Basel.)
- Published
- 2016
- Full Text
- View/download PDF