title: SGK1, the New Player in the Game of Resistance: Chemo-Radio Molecular Target and Strategy for Inhibition.
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.
authors: Department of "Scienze della Salute", University "Magna Græcia" of Catanzaro, Viale Europa, Catanzaro, Italy.
authors: Cristina
authors: C
authors: Talarico
authors: Vincenzo
authors: V
authors: Dattilo
authors: Lucia
authors: L
authors: D'Antona
authors: Miranda
authors: M
authors: Menniti
authors: Cataldo
authors: C
authors: Bianco
authors: Francesco
authors: F
authors: Ortuso
authors: Stefano
authors: S
authors: Alcaro
authors: Silvia
authors: S
authors: Schenone
authors: Nicola
authors: N
authors: Perrotti
authors: Rosario
authors: R
authors: Amato
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005720:Gamma Rays / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011836:Radiation Tolerance / Q000235:genetics; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000970:Antineoplastic Agents; D020169:Caspases; D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D007527:Isoenzymes; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D000099184:Serum-Glucocorticoid Regulated Kinases