Anti-apoptotic hPEBP4 silencing promotes TRAIL-induced apoptosis of human ovarian cancer cells by activating ERK and JNK pathways

Peng Li, Xiaojian Wang, Nan Li, Huabei Kong, Zhenhong Guo, Shuxun Liu, Xuetao Cao
2006 International Journal of Molecular Medicine  
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cell lines but not typically in normal or nontransformed cells, which makes TRAIL a desirable therapeutic agent to fight cancer. Human phosphatidylethanolamine-binding protein 4 (hPEBP4) is a recently identified anti-apoptotic molecule and has been shown to be highly expressed in breast and ovarian cancer cells. We demonstrate that silencing of hPEBP4 in CaoV-3 ovarian cancer cells
more » ... TRAIL-induced apoptosis. We found that endogenous hPEBP4 interacts with Raf-1 and MEK1 in TRAIL-treated CaoV-3 cells by coimmunoprecipitation analysis. Simultaneously, silencing of hPEBP4 in CaoV-3 cells enhances TRAIL-induced ERK and JNK activation. Moreover, the inhibitors of MEK1 or JNK can reduce hPEBP4-silence-induced TRAIL sensitivity. Therefore, silencing of hPEBP4 in CaoV-3 ovarian cancer promotes TRAIL-induced apoptosis, and the increased MAPK activation is required for the apoptosis sensitization. All these data indicate that silencing of hPEBP4, an important potential target, may be a promising approach for the treatment of ovarian cancer.
doi:10.3892/ijmm.18.3.505 fatcat:usrzq35cj5fejmb7ljnfahxwu4