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Mini Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2019.00018

Salt-inducible kinase 2: an oncogenic signal transmitter and potential application as a new therapeutic target for cancers

 Fangyu Chen1, 2, Liuwei Chen2, Qin Qin1 and  Xinchen Sun1*
  • 1Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, China
  • 2First Clinical Medical College, Nanjing Medical University, China

The salt-inducible kinase (SIK), which belongs to the sucrose non-fermenting 1 and AMP-activated protein kinase (SNF1/AMPK), is first discovered in the adrenal cortex of a rat on a high-salt diet. As an isoform of the SIK family, SIK2 modulates various biological functions and acts as signal transmitters in different pathways. Compared with adjacent normal tissues, the expression of SIK2 is significantly higher in multiple types of tumor, indicating its pivotal effect in oncogenesis. Recently, a series of studies about SIK2 have emerged to underline its role in several signaling pathways, including PI3K-Akt-mTOR pathway, Hippo-YAP pathway, LKB1-HDAC axis and cAMP-PKA axis. Moreover, a few small-molecule SIK2 inhibitors are found to be able to rescue the oncogenicity of SIK2 during tumor development and reverse its abnormal activation of downstream pathways. However, SIK2 inhibitors may have potential pro-tumor side effect. In this mini-review, we will discuss the results of in vivo and in vitro studies regarding SIK2 mechanism in different signaling pathways, and particularly their regulation in cancer cells. This may provide new ideas for targeting SIK2 as a new therapeutic strategy in tumor therapy.

Keywords: SIK2, Cancer, signaling pathway, target therapy, chemosensitivity, radiosensitivity

Received: 09 Oct 2018; Accepted: 07 Jan 2019.

Edited by:

Zhe-Sheng Chen, St. John's University, United States

Reviewed by:

Luca Tamagnone, Institute for Cancer Research and Treatment (IRCC), Italy
Yun Dai, Virginia Commonwealth University, United States
Xingxiang Pu, Hunan Cancer Hospital, China  

Copyright: © 2019 Chen, Chen, Qin and Sun. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Xinchen Sun, Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China,