MAGI-2 Inhibits cell migration and proliferation via PTEN in human hepatocarcinoma cells

• Published in: Archives of biochemistry and biophysics Vol. 467; no. 1; pp. 1 - 9
• Main Authors: Hu, Yali, Li, Zengxia, Guo, Liang, Wang, Liying, Zhang, Lineng, Cai, Xiumei, Zhao, Hongbo, Zha, Xiliang
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2007
• Subjects: Carcinoma, Hepatocellular - metabolism; Carrier Proteins; Cell migration; Cell Movement; Cell Proliferation; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Gene Expression Regulation, Neoplastic; Human hepatocarcinoma cell lines; Humans; Liver Neoplasms - metabolism; MAGI-2; Models, Biological; Phosphorylation; Plasmids - metabolism; Protein Structure, Tertiary; Proteins - metabolism; Proteins - physiology; PTEN; PTEN Phosphohydrolase - metabolism; RNA, Messenger - metabolism; Transfection; Cell proliferation; PTEN; MAGI-2; Human hepatocarcinoma cell lines; Cell migration
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2007.07.027

MAGI-2, a multidomain scaffolding protein, contains nine potential protein–protein interaction modules, including a GuK domain, two WW domains and six PDZ domains. In this study, we examined eight human hepatocarcinoma cell lines (HHCCs) and found that MAGI-2 was expressed only in 7721 cells. After 7721, 7404 and 97H cells were transfected with myc-MAGI-2 plasmid, their migration and proliferation was significantly inhibited, which was associated with downregulation of p-FAK and p-Akt. It is known that p-FAK is a substrate of PTEN and p-Akt can be regulated by PTEN via PIP3. We demonstrated that PTEN was upregulated after myc-MAGI-2 transfection, which was due to the enhancement of PTEN protein stability rather than mRNA levels. Furthermore, MAGI-2-induced inhibition of cell migration and proliferation was attenuated in 7721 cells with PTEN silence or in PTEN-null cell line U87MG, and PTEN transfection could restore the effect of MAGI-2 in U87MG cells. Finally, the molecular association between PTEN and MAGI-2 was confirmed. Our results suggested that PTEN played a critical role in MAGI-2-induced inhibition of cell migration and proliferation in HHCCs.