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Salt-Inducible Kinase 2: An Oncogenic Signal Transmitter and Potential Target for Cancer Therapy
Fangyu Chen1,2, Liuwei Chen2, Qin Qin1
1Department of Radiation Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Abstract:
Salt-inducible kinase (SIK), which belongs to the sucrose non-fermenting 1/AMP-activated protein kinase family, was 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 a signal transmitter in various pathways. Compared with that in adjacent normal tissues, the expression of SIK2 is significantly higher in multiple types of tumors, which indicates its pivotal effect in oncogenesis. Studies on SIK2 have recently underlined its role in several signaling pathways, including the PI3K-Akt-mTOR pathway, the Hippo-YAP pathway, the LKB1-HDAC axis, and the cAMP-PKA axis. Moreover, a few small-molecule SIK2 inhibitors have been found to be able to rescue the oncogenicity of SIK2 during tumor development and reverse its abnormal activation of downstream pathways. In this mini-review, we discuss the results of in vivo and in vitro studies regarding the SIK2 mechanism in different signaling pathways, particularly their regulation of cancer cells. This work may provide new ideas for targeting SIK2 as a novel therapeutic strategy in tumor therapy.
Insights
Salt-inducible kinase 2 (SIK2) is upregulated in many cancers and drives oncogenesis through key signaling pathways. Inhibiting SIK2 shows promise as a novel cancer therapy by reversing its abnormal activation.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Salt-inducible kinase 2 (SIK2) is an important signaling molecule.
- SIK2 expression is elevated in various tumor types, suggesting a role in cancer development.
- SIK2 participates in critical cellular signaling pathways.
Purpose of the Study:
- To review the role of SIK2 in cancer.
- To discuss SIK2's involvement in key signaling pathways.
- To explore SIK2 as a therapeutic target in oncology.
Main Methods:
- Review of in vivo and in vitro studies.
- Analysis of SIK2's mechanism in different signaling pathways.
- Examination of SIK2's regulation of cancer cells.
Main Results:
- SIK2 significantly impacts oncogenesis.
- SIK2 regulates crucial pathways like PI3K-Akt-mTOR and Hippo-YAP.
- Small-molecule SIK2 inhibitors demonstrate potential in preclinical studies.
Conclusions:
- SIK2 plays a pivotal role in cancer cell regulation.
- Targeting SIK2 offers a potential novel therapeutic strategy for cancer treatment.
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