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

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 PIP(3). 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.