Effect of Mst1 overexpression on the growth of human hepatocellular carcinoma HepG2 cells and the sensitivity to cisplatin in vitro

Chuanming Xu, Chunju Liu, Wei Huang, Shuo Tu and Fusheng Wan

Acta Biochim Biophys Sin (Shanghai). 2013 Apr;45(4):268-79. doi: 10.1093/abbs/gmt006

Department of Biochemistry and Molecular Biology, Basic Medical College of Nanchang University, Nanchang 330006, China

Mammalian STE20-like kinase 1 (Mst1) is the mammalian homologue of Drosophila Hippo, a major inhibitor of cell proliferation in Drosophila. It ubiquitously encodes serine threonine kinase that belongs to the family of protein kinases related to yeast STE20, and is involved in cell proliferation, apoptosis, oncogenesis, and organ growth. Recent studies have shown that Mst1 has tumor-suppressor function, and the deletion or mutation of Mst1 is reported to be associated with tumorigenesis. To investigate the effect of overexpression of Mst1 on the growth of human liver cancer cell line HepG2cells and the sensitivity to cisplatin in vitro, here we constructed recombinant eukaryotic expression vector pEGFP-N1-Mst1 containing Mst1 gene, and transiently transfected into HepG2cells. The effects of Mst1overexpression on the cell proliferation and apoptosis, the phosphorylation status of Yes-associated protein, and the mRNA transcript levels of connective tissue growth factor (CTGF), amphiregulin (AREG), and birc5 (Survivin) were determined. Results showed that overexpression of Mst1 inhibited cell proliferation, induced apoptosis of HepG2cells, promoted YAP (Ser127) phosphorylation, and downregulated the mRNA expression of CTGF, AREG, and Survivin. We also investigated the relationship between the expression and cleavage of Mst1 and cisplatin-induced cell death. We found that Mst1overexpression could induce cisplatin chemosensitivity, and cisplatin could promote the cleavage of Mst1 without affecting the expression of Mst1. Overall, our results indicated that Mst1 might be a promising anticancer target.

图例: cisplatin、Mst1、YAP1、p53和p73的相互关系

全文: http://abbs.oxfordjournals.org/content/45/4/268.full

引用本文的文献:

1 Expression and Clinical Significance of YAP, TAZ, and AREG in Hepatocellular Carcinoma

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