Downregulation of cPLA2γ expression inhibits EGF-induced chemotaxis of human breast cancer cells through Akt pathway

作者：Tian, Gang; Wang, Xueqian; Zhang, Fei; Geng, Hua; Hou, Wei; Chen, Liwei; Guo, Hua^*; Zhang, Ning

来源：Biochemical and Biophysical Research Communications, 2011, 409(3): 506-512.

DOI：10.1016/j.bbrc.2011.05.035

• cPLA(2)gamma
• Breast cancer
• Chemotaxis
• EGF
• Akt

Phospholipids play an important role in mediating cell migration. In the present study, we investigated the role of cPLA(2)gamma in chemotaxis of human breast cancer cells. Inhibition of cPLA(2)gamma expression by small interference RNA severely inhibits EGF-induced chemotaxis in a dose-dependent manner in MDA-MB-231, MCF-7, T47D and ZR-75-30 cells. Furthermore, silencing cPLA(2)gamma expression also impaired directional migration, adhesion and invasion in MDA-MB-231 cells. In addition, we investigated the molecular mechanism by which cPLA(2)gamma regulated migration. Knockdown of cPLA(2)gamma suppressed the phosphorylation of Akt at both Thr308 and Ser473. Phosphorylation of PKC zeta, downstream of Akt, was also dampened. Knockdown of cPLA(2)gamma also impaired the phosphorylation of integrin beta 1 and cofilin, key regulators of cell adhesion and actin polymerization, respectively. Taken together, our results suggest that cPLA(2)gamma plays an important role in cancer cell chemotaxis.

• 出版日期2011-6-10
• 单位天津医科大学; 天津市天津医院