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Mst1 overexpression inhibited the growth of human non-small cell lung cancer in vitro and in vivo

Cancer Gene Therapy volume 20, pages 453–460 (2013)Cite this article

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Abstract

Mammalian STE20-like kinase 1 (Mst1) ubiquitously encodes serine threonine kinase, which is a 59-kDa class II GC kinase that shares 76% identity in amino-acid sequence with MST2, and is the closest mammalian homolog of Drosophila Hippo protein kinase, a major inhibitor of cell proliferation in Drosophila. Recent studies have shown that Mst1 and Mst2 perform tumor-suppressor function in a redundant manner and were originally identified as pro-apoptotic cytoplasmic kinases important for controlling cell growth, proliferation, apoptosis and organ size. We used recombinant eukaryotic expression vector containing human wild-type Mst1 gene to transfect human non-small cell lung cancer (NSCLC) A549 cells in vitro and in vivo. The results showed that Mst1 overexpression inhibited cell proliferation and induced apoptosis of A549 cells, promoted Yes-associated protein (YAP) (Ser127) phosphorylation and downregulated the transcriptional level of Cystein-rich protein connective tissue growth factor (CTGF), amphiregulin (AREG) and Survivin. In human NSCLC-cell-A549-xenograft models, Mst1 gene or cisplatin alone suppressed the growth of tumors and increased the cytoplasm-positive expression levels of YAP and Phospho-YAP (Ser127) proteins; however, their combination had the strongest anticancer effects. Overall, Mst1 has an important role in inhibiting the growth of NSCLC in vitro and in vivo; its antiproliferative effect is associated with induction of apoptosis through promotion of the cytoplasmic localization and phosphorylation of YAP protein at Ser127 site, indicating that Mst1 may be developed as a promising therapeutic target for NSCLC.

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Acknowledgements

This work was supported by the grants from the National Natural Science Foundation of China (no. 30060029) and the Natural Science Foundation of Jiangxi Province (no. 2010JXY0237).

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  1. C M Xu and W W Liu: These authors are joint first authors.

Authors and Affiliations

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

    C M Xu, W W Liu, C J Liu, C Wen, H F Lu & F S Wan

  2. Department of Animal Science, Nanchang University, Nanchang, China

    F S Wan

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Correspondence to F S Wan.

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Xu, C., Liu, W., Liu, C. et al. Mst1 overexpression inhibited the growth of human non-small cell lung cancer in vitro and in vivo. Cancer Gene Ther 20, 453–460 (2013). https://doi.org/10.1038/cgt.2013.40

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