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.
Hu
Yali
Y
Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032, PR China.
Li
Zengxia
Z
Guo
Liang
L
Wang
Liying
L
Zhang
Lineng
L
Cai
Xiumei
X
Zhao
Hongbo
H
Zha
Xiliang
X
D048868:Adaptor Proteins, Signal Transducing; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002352:Carrier Proteins; D002465:Cell Movement; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D051528:Guanylate Kinases; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008954:Models, Biological; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D011506:Proteins; D012333:RNA, Messenger; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human