The increasing role of pigment epithelium-derived factor in metastasis: from biological importance to a promising target

Pigment epithelium-derived factor (PEDF) is a non-inhibitory member of the serpin (serine protease inhibitor) family and is a well-known potent anti-tumor factor in a variety of cancers. It has been ascertained that PEDF regulates multiple metastatic processes through various plausible mechanisms, including inhibiting angiogenesis, inducing apoptosis, stimulating extracellular matrix (ECM) degradation, and suppressing the epithelial-tomesenchymal transition (EMT) process. Although PEDF has been recognized as an anti-metastatic marker in most studies, its role remains controversial with conflicting reports of PEDF as a metastatic marker. The emerging insights into the mechanism(s) of PEDF in tumor progression and its therapeutic effects are discussed systematically in this review, aiming to improve our understanding in the context of metastasis and drug development.