PMID- 23419720 OWN - NLM STAT- MEDLINE DCOM- 20130917 LR - 20211203 IS - 1745-7270 (Electronic) IS - 1672-9145 (Linking) VI - 45 IP - 4 DP - 2013 Apr TI - Effect of Mst1 overexpression on the growth of human hepatocellular carcinoma HepG2 cells and the sensitivity to cisplatin in vitro. PG - 268-79 LID - 10.1093/abbs/gmt006 [doi] AB - 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 HepG2 cells and the sensitivity to cisplatin in vitro, here we constructed recombinant eukaryotic expression vector pEGFP-N1-Mst1 containing Mst1 gene, and transiently transfected into HepG2 cells. The effects of Mst1 overexpression 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 HepG2 cells, 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 Mst1 overexpression 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. FAU - Xu, Chuanming AU - Xu C AD - Department of Biochemistry and Molecular Biology, Basic Medical College of Nanchang University, Nanchang 330006, China. FAU - Liu, Chunju AU - Liu C FAU - Huang, Wei AU - Huang W FAU - Tu, Shuo AU - Tu S FAU - Wan, Fusheng AU - Wan F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130217 PL - China TA - Acta Biochim Biophys Sin (Shanghai) JT - Acta biochimica et biophysica Sinica JID - 101206716 RN - 0 (AREG protein, human) RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Amphiregulin) RN - 0 (Antineoplastic Agents) RN - 0 (BIRC5 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 (Phosphoproteins) RN - 0 (Survivin) RN - 0 (Transcription Factors) RN - 0 (YAP-Signaling Proteins) RN - 0 (YAP1 protein, human) 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) RN - Q20Q21Q62J (Cisplatin) SB - IM EIN - Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):801 MH - Adaptor Proteins, Signal Transducing/genetics/metabolism MH - Amphiregulin MH - Antineoplastic Agents/pharmacology MH - Apoptosis/*drug effects MH - Blotting, Western MH - Carcinoma, Hepatocellular/genetics/metabolism/pathology MH - Cell Proliferation/*drug effects MH - Cisplatin/*pharmacology MH - Connective Tissue Growth Factor/genetics/metabolism MH - Down-Regulation/drug effects MH - EGF Family of Proteins MH - Gene Expression Regulation, Neoplastic MH - Glycoproteins/genetics/metabolism MH - Hep G2 Cells MH - Humans MH - Inhibitor of Apoptosis Proteins/genetics/metabolism MH - Intercellular Signaling Peptides and Proteins/genetics/metabolism MH - Intracellular Signaling Peptides and Proteins MH - Liver Neoplasms/genetics/metabolism/pathology MH - Microscopy, Fluorescence MH - Phosphoproteins/genetics/metabolism MH - Phosphorylation/drug effects MH - Protein Serine-Threonine Kinases/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Survivin MH - Transcription Factors MH - YAP-Signaling Proteins EDAT- 2013/02/20 06:00 MHDA- 2013/09/18 06:00 CRDT- 2013/02/20 06:00 PHST- 2013/02/20 06:00 [entrez] PHST- 2013/02/20 06:00 [pubmed] PHST- 2013/09/18 06:00 [medline] AID - gmt006 [pii] AID - 10.1093/abbs/gmt006 [doi] PST - ppublish SO - Acta Biochim Biophys Sin (Shanghai). 2013 Apr;45(4):268-79. doi: 10.1093/abbs/gmt006. Epub 2013 Feb 17.