Ran Jianhua,Zhong Dong,Tang Yun,Chen Guijie,Li Xiaosong,Zhang Xiaodong.Molecular mechanism of Syntenin promoting human glioma cell migration though upregulating FAK phosphorylation[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(10):943-947.
Ran Jianhua,Zhong Dong,Tang Yun,Chen Guijie,Li Xiaosong,Zhang Xiaodong.Molecular mechanism of Syntenin promoting human glioma cell migration though upregulating FAK phosphorylation[J].J Amry Med Univ (J Third Mil Med Univ),2012,34(10):943-947.DOI:
Objective To investigate the molecular mechanism of Syntenin promoting human glioma cell migration. Methods The migration ability tests of CHG-5 cells (human glioma cell line) and CHG-hS cells (CHG-5 stably expression human Syntenin) on fibronectin (FN) and poly-L-lysine (PL) were performed by scratch wound assay. FAK phosphorylation and activation of its relative signal molecules JNK
AKT and Src were detected by Western blotting. After CHG-hS and CHG-5 cells were treated with P38 MAPK specific inhibitor SB239063 and PI3K specific inhibitor LY294002
respectively
the migration ability of the cells on FN was investigated by scratch wound assay and the phosphorylation levels of JNK and AKT were detected by Western blotting. Results The result of scratch wound assay showed that the migration ability of the CHG-hS cells on FN-coated plates was significantly higher than that of the CHG-5 cells (P0.05)
while the migration ability of the CHG-hS cells on PL-coated plates showed no significant difference compared with that of the CHG-5 cells (P0.05). Western blot analysis showed that the phosphorylation levels of FAK phosphorylation sites (Tyr397
Tyr576
Tyr925
but not Tyr861) and FAK-related signal molecules (phosphor-Src
phosphor-JNK and phosphor-AKT) in the CHG-hS cells on FN increased in a time-dependent manner (P0.05). The migration ability of the CHG-hS cells decreased along with the reduced levels of phosphor-JNK and phosphor-AKT after treated with SB239063 and LY294002
respectively. Conclusion Syntenin specifically interacting with p-Src promotes the phosphorylation of FAK Tyr397
Tyr925 and Tyr576
which activates FAK to a maximum extent and upregulates the phosphorylation levels of downstream signal molecules such as JNK and AKT
and finally promotes FN-related glioma cell migration though the Syntenin-Src/FAK/MAPK and Syntenin-Src/FAK/PI3K pathways.