Pigment epithelium-derived factor and its phosphomimetic mutant induce JNK-dependent apoptosis and p38-mediated migration arrest.

ABSTRACT: Pigment epithelium-derived factor (PEDF) is a potent endogenous inhibitor of angiogenesis and a promising anticancer agent. We have previously shown that PEDF can be phosphorylated and that distinct phosphorylations differentially regulate its physiological functions. We also demonstrated that triple phosphomimetic mutant (EEE-PEDF), has significantly increased antiangiogenic activity and is much more efficient than WT-PEDF in inhibiting neovascularization and tumor growth. The enhanced antiangiogenic effect was associated with a direct ability to facilitate apoptosis of tumor-residing endothelial cells (ECs), and subsequently, disruption of intratumoral vascularization. In the present report, we elucidated the molecular mechanism by which EEE-PEDF exerts more profound effects at the cellu

SUBMITTER: Konson A 

PROVIDER: S-EPMC3030359 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature