TY - JOUR
T1 - Downregulation of cPLA2γ expression inhibits EGF-induced chemotaxis of human breast cancer cells through Akt pathway
AU - Tian, Gang
AU - Wang, Xueqian
AU - Zhang, Fei
AU - Geng, Hua
AU - Hou, Wei
AU - Chen, Liwei
AU - Guo, Hua
AU - Zhang, Ning
PY - 2011/6/10
Y1 - 2011/6/10
N2 - Phospholipids play an important role in mediating cell migration. In the present study, we investigated the role of cPLA2γ in chemotaxis of human breast cancer cells. Inhibition of cPLA2γ 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 cPLA2γ expression also impaired directional migration, adhesion and invasion in MDA-MB-231 cells. In addition, we investigated the molecular mechanism by which cPLA2γ regulated migration. Knockdown of cPLA2γ suppressed the phosphorylation of Akt at both Thr308 and Ser473. Phosphorylation of PKCζ, downstream of Akt, was also dampened. Knockdown of cPLA2γ also impaired the phosphorylation of integrin β1 and cofilin, key regulators of cell adhesion and actin polymerization, respectively. Taken together, our results suggest that cPLA2γ plays an important role in cancer cell chemotaxis.
AB - Phospholipids play an important role in mediating cell migration. In the present study, we investigated the role of cPLA2γ in chemotaxis of human breast cancer cells. Inhibition of cPLA2γ 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 cPLA2γ expression also impaired directional migration, adhesion and invasion in MDA-MB-231 cells. In addition, we investigated the molecular mechanism by which cPLA2γ regulated migration. Knockdown of cPLA2γ suppressed the phosphorylation of Akt at both Thr308 and Ser473. Phosphorylation of PKCζ, downstream of Akt, was also dampened. Knockdown of cPLA2γ also impaired the phosphorylation of integrin β1 and cofilin, key regulators of cell adhesion and actin polymerization, respectively. Taken together, our results suggest that cPLA2γ plays an important role in cancer cell chemotaxis.
KW - Akt
KW - Breast cancer
KW - CPLAγ
KW - Chemotaxis
KW - EGF
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UR - http://www.scopus.com/inward/citedby.url?scp=79958190154&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2011.05.035
DO - 10.1016/j.bbrc.2011.05.035
M3 - Article
C2 - 21600875
AN - SCOPUS:79958190154
VL - 409
SP - 506
EP - 512
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -