Phospholipase D (PLD) has emerged as a critical element in the cell growth signaling. Despite extensive information regarding the regulation of PLD activity in cell survival, the signaling mechanisms that regulate PLD expression in cancer remains poorly understood. Here we investigate that platelet derived growth factor (PDGF) increases PLD1 but not PLD2 expression via Ras-ERK/PI3K-NFκB signaling cascade in SK-BR3 breast cancer cells. The two NFκB-binding sites are functionally critical for transcriptional activation of PLD1 induced by PDGF. Furthermore, depletion of PLD1 using siRNA significantly abolished PDGF-induced upregulation of matrix metalloproteinase-2 or -9 and invasion of breast cancer cells. Thus, we propose that PDGF-induced PLD1 expression via NFκB signaling pathway might contribute to carcinogenesis.
Bibliographical noteFunding Information:
This work was supported by a grant from Translational Research Center for Protein Function Control , NSF (2009-0092960) , South Korea, and by a grant from the Nation R&D Program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea (0920050) .
All Science Journal Classification (ASJC) codes
- Cancer Research