Pigment epithelium-derived factor (PEDF) plays an important role in the
tumor growth and
metastasis inhibition. It has been reported that PEDF expression is significantly reduced in
breast cancer, and associated with
disease progression and poor patient outcome. However, the exact mechanism of PEDF on
breast cancer metastasis including liver and lung
metastasis remains unclear. The present study aims to reveal the impact of PEDF on
breast cancer. The orthotopic
tumor mice model inoculated by MDA-MB-231 cells stably expressing PEDF or control cells was used to assess liver and lung
metastasis of
breast cancer. In vitro, migration and invasion experiments were used to detect the metastatic abilities of MDA-MB-231 and SKBR3
breast cancer cells with or without overexpression of PEDF. The metastatic-related molecules including EMT makers,
fibronectin, and p-AKT and p-ERK were detected by qRT-PCR, Western blot, and Fluorescent immunocytochemistry. PEDF significantly inhibited
breast cancer growth and
metastasis in vivo and in vitro. Mechanically, PEDF inhibited
breast cancer cell migration and invasion by down-regulating
fibronectin and subsequent MMP2/MMP9 reduction via p-ERK and p-AKT signaling pathways. However, PEDF had no effect on EMT conversion in the
breast cancer cells which was usually involved in
cancer metastasis. Furthermore, the study showed that
laminin receptor mediated the down-regulation of
fibronectin by PEDF. These results reported for the first time that PEDF inhibited
breast cancer metastasis by down-regulating
fibronectin via
laminin receptor/AKT/ERK pathway. Our findings demonstrated PEDF as a dual effector in limiting
breast cancer growth and
metastasis and highlighted a new avenue to block
breast cancer progression.