The diverse oncogenic and tumor suppressor roles of salt-inducible kinase (SIK) in cancer.

INTRODUCTION: The salt-inducible kinases originally cloned in adrenal glands of high salt diet-fed rats, generally named as SIKs, are highly evolutionarily conserved serine/threonine protein kinases belonging to a family of AMP-activated protein kinase (AMPK). Overexpression of SIK2 and SIK3 is discovered in many tumors. Whereas, SIK1 expression was significantly lower in tumors than in normal tissues. AREAS COVERED: The main aim of our review is to introduce the signaling pathways as well as its mechanisms underlying their activity regulation, and especially the roles they play in cancer, which may shed light on the prospects of the cancer prevention and therapeutic targeting of SIKs in the future. EXPERT OPINION: It is conceivable that SIKs, mainly stimulated by ACTH, LKB1, TGF-β, and autophosphorylation, play crucial roles in regulating multiple signal pathways in cancer cells and controlling a series of cellular processes including cell proliferation and cell apoptosis. More recent studies about SIKs are emerging, and their overexpression is found in a few specific types of cancers. However, correlations between SIKs and carcinogenesis remain to be fully elucidated.