The role of Salt-inducible kinase 2 in hepatocellular carcinoma

Abstract

Salt-inducible kinase 2 (SIK2) has been shown to associate with cancer formation. However, its role in tumorigenicity remains controversial. It has been reported to promote proliferation of ovarian cancer cells, but inhibit growth of breast cancer cells (1). In my project, I aim to characterize the role of SIK2 in hepatocellular carcinoma (HCC). Using Matrigel invasion assay, I showed that SIK2 overexpression promoted cell invasion in HCC cells despite lack of effects on cell proliferation and migration. Meanwhile, knockdown of SIK2 by siRNA inhibited invasion. To understand the molecular mechanism, epithelial–mesenchymal transition (EMT) markers were screened. Western analysis revealed that SIK2 overexpression upregulated mesenchymal marker N-cadherin while it downregulated epithelial marker β-catenin. Consistently, qPCR result confirmed that N-cadherin transcripts were increased after SIK2 overexpression. Besides, the transcripts of matrix metallopeptidase 2 (MMP2) also increases with SIK2 overexpression. Recently, SIK2 has been identified as a centrosomal kinase. I found that the phosphorylated and active form of SIK2 has a preferential localization to the centrosome. In short, SIK2 promotes HCC invasion by enhancing EMT and MMP2 secretion. However, the downstream signalling partner of SIK2 has yet to be determined. Immunoprecipitation followed by mass spectroscopy will be employed to answer the question.