1. Spindle and kinetochore-associated protein 2 facilitates the proliferation and invasion of hepatocellular carcinoma via the regulation of Wnt/β-catenin signaling.
- Author
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Jiang, Jiong, Xu, Bing, Zheng, Ying, Guo, Xiaoyan, and Chen, Fenrong
- Subjects
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HEPATOCELLULAR carcinoma , *CATENINS , *MULTIPLE tumors , *WNT proteins , *TUMOR growth , *CANCER invasiveness , *CELL growth - Abstract
Recent studies have shown that spindle and kinetochore-associated protein 2 (SKA2) is dysregulated in multiple tumors and acts as a key regulator of tumor progression. However, whether SKA2 plays a role in hepatocellular carcinoma (HCC) has not been fully elucidated. The purpose of this study was to explore the expression, function and underlying molecular mechanism of SKA2 in HCC. We found that SKA2 was highly expressed in HCC tissues and cell lines. Knockdown of SKA2 caused marked reductions in the proliferative, colony-forming and invasive capacities of HCC cells, while SKA2 overexpression had opposite effects. Further experiments revealed that overexpression of SKA2 enhanced expression levels of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin in HCC cells. Moreover, SKA3 overexpression enhanced transcriptional activity mediated by Wnt/β-catenin signaling. Knockdown of SKA3 downregulated the activation of Wnt/β-catenin signaling, and the effect was significantly reversed by the inhibition of GSK-3β. Notably, inhibition of Wnt/β-catenin signaling markedly abrogated SKA2-mediated promotion effect on HCC proliferation and invasion. In addition, knockdown of SKA2 impeded tumor formation and growth in HCC cells in a nude mouse in vivo model. Overall, these findings indicate that SKA2 accelerates the progression of HCC through the upregulation of Wnt/β-catenin signaling. Our study highlights a potential role of SKA2 in HCC progression and suggests it as a possible target for HCC treatment. Image 1 • SKA2 is highly expressed in HCC. • SKA2 knockdown inhibits proliferation and invasion in HCC cells. • SKA2 promotes Wnt/β-catenin via modulation of GSK-3β. • SKA2 exerts the function in HCC cells by Wnt/β-catenin signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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