PMID- 23928732 OWN - NLM STAT- MEDLINE DCOM- 20140603 LR - 20211203 IS - 1476-5500 (Electronic) IS - 0929-1903 (Linking) VI - 20 IP - 8 DP - 2013 Aug TI - Mst1 overexpression inhibited the growth of human non-small cell lung cancer in vitro and in vivo. PG - 453-60 LID - 10.1038/cgt.2013.40 [doi] AB - 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. FAU - Xu, C M AU - Xu CM AD - Department of Biochemistry and Molecular Biology, Basic Medical College of Nanchang University, Nanchang, China. FAU - Liu, W W AU - Liu WW FAU - Liu, C J AU - Liu CJ FAU - Wen, C AU - Wen C FAU - Lu, H F AU - Lu HF FAU - Wan, F S AU - Wan FS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130809 PL - England TA - Cancer Gene Ther JT - Cancer gene therapy JID - 9432230 RN - 0 (AREG protein, human) RN - 0 (Amphiregulin) RN - 0 (Areg protein, mouse) RN - 0 (BIRC5 protein, human) RN - 0 (CCN2 protein, human) RN - 0 (EGF Family of Proteins) RN - 0 (Glycoproteins) RN - 0 (Inhibitor of Apoptosis Proteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (Survivin) RN - 139568-91-5 (Connective Tissue Growth Factor) RN - EC 2.7.1.11 (STK4 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Amino Acid Sequence MH - Amphiregulin MH - Animals MH - Apoptosis/physiology MH - Carcinoma, Non-Small-Cell Lung/*enzymology/genetics/pathology MH - Cell Growth Processes/physiology MH - Connective Tissue Growth Factor/biosynthesis/genetics MH - EGF Family of Proteins MH - Female MH - Gene Transfer Techniques MH - Glycoproteins/biosynthesis/genetics MH - Heterografts MH - Humans MH - Inhibitor of Apoptosis Proteins/biosynthesis/genetics MH - Intercellular Signaling Peptides and Proteins/biosynthesis/genetics MH - Intracellular Signaling Peptides and Proteins MH - Lung Neoplasms/*enzymology/genetics/pathology MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Molecular Sequence Data MH - Protein Serine-Threonine Kinases/*biosynthesis/genetics MH - Signal Transduction MH - Survivin MH - Transfection EDAT- 2013/08/10 06:00 MHDA- 2014/06/04 06:00 CRDT- 2013/08/10 06:00 PHST- 2013/05/15 00:00 [received] PHST- 2013/05/19 00:00 [accepted] PHST- 2013/08/10 06:00 [entrez] PHST- 2013/08/10 06:00 [pubmed] PHST- 2014/06/04 06:00 [medline] AID - cgt201340 [pii] AID - 10.1038/cgt.2013.40 [doi] PST - ppublish SO - Cancer Gene Ther. 2013 Aug;20(8):453-60. doi: 10.1038/cgt.2013.40. Epub 2013 Aug 9.