a Jiangsu Key Laboratory of Biological Cancer Therapy , Xuzhou Medical College , Xuzhou 221002 , China.
b Center of Clinical Oncology , Affiliated Hospital of Xuzhou Medical College , Xuzhou 221002 , China.
Expert Opin Ther Targets. 2016;20(4):477-85. doi: 10.1517/14728222.2016.1101452. Epub 2015 Nov 7.
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.
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.
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.
最初在高盐饮食喂养的大鼠肾上腺中克隆的盐诱导激酶，通常称为 SIKs，是高度进化保守的丝氨酸/苏氨酸蛋白激酶，属于 AMP 激活蛋白激酶（AMPK）家族。在许多肿瘤中发现 SIK2 和 SIK3 的过表达。然而，SIK1 在肿瘤中的表达明显低于正常组织。
我们综述的主要目的是介绍信号通路及其活性调节机制，特别是它们在癌症中的作用，这可能为未来 SIKs 在癌症预防和治疗靶向方面的前景提供启示。
可以想象，SIKs 主要受 ACTH、LKB1、TGF-β 和自身磷酸化的刺激，在调节癌细胞中的多种信号通路以及控制包括细胞增殖和细胞凋亡在内的一系列细胞过程中发挥关键作用。关于 SIKs 的更多最新研究正在出现，并且在少数特定类型的癌症中发现了它们的过表达。然而，SIKs 与致癌作用之间的相关性仍有待充分阐明。
