Identification of the role of Smad interacting protein 1 (SIP1) in glioma.
Glioma is an extremely aggressive and lethal form of brain cancer. Despite recent advances in diagnostics and treatments, prognosis for advanced patients suffering from these diseases remains poor. Therefore, identification of new therapeutic targets for glioma is of significant importance. In this study, we identified the important role of Smad interacting protein 1 (SIP1; also known as ZEB2) in glioma. We firstly found that SIP1 expression was high in four tumorigenic glioma cell lines but low in two nontumorigenic glioma cell lines. By knockdown or overexpression assay, we discovered that knockdown of SIP1 expression statistically significantly inhibited cell migration and invasion of tumorigenic glioma cells, while overexpression of SIP1 promoted cell migration and invasion of nontumorigenic glioma cells. SIP1 knockdown inhibits and overexpression promotes glioma cell clonogenicity in vitro. Further studies identified that SIP1 overexpression inhibits expression of E-cadherin and enhances expression of mesenchymal proteins such as fibronectin and vimentin. This study supports the rationale for developing SIP1 as a potential therapeutic and diagnostic target for gliomas.
Xia
Microgene
M
Integrative Laboratory, The University of Hong Kong, Pokfulam, Hong Kong, China. microgene82@gmail.com
Hu
Minghua
M
Wang
Jun
J
Xu
Yajun
Y
Chen
Xiaobing
X
Ma
Yuedong
Y
Su
Lei
L
D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism*; D015820:Cadherins; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005910:Glioma / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D015820:Cadherins; C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins