Roles of salt-inducible kinases in cancer (Review)

Salt inducible kinases (SIKs) with three subtypes SIK1, SIK2 and SIK3, belong to the AMP-activated protein kinase family. They are expressed ubiquitously in humans. Under normal circumstances, SIK1 regulates adrenocortical function in response to high salt or adrenocorticotropic hormone stimulation, SIK2 is involved in cell metabolism, controlling insulin signaling and gluconeogenesis and SIK3 coordinates with the mTOR complex, promoting cancer. The dysregulation of SIKs has been widely detected in various types of cancers. Based on most of the existing studies, SIK1 is mostly considered a tumor inhibitor, SIK2 and SIK3 are usually associated with tumor promotion. However, the functions of SIKs have shown contradictory in certain tumors, suggesting that SIKs cannot be simply classified as oncogenes or tumor suppressor genes. The present review provided a comprehensive summary of the roles of SIKs in the initiation and progression of different cancers, aiming to elucidate their clinical value and discuss potential strategies for targeting SIKs in cancer therapy.