PIP3‐dependent Rac exchanger 1 (P‐Rex1) promotes prostate cancer cell migration

Abstract

Activation of Rac by guanine-nucleotide exchange factors (GEFs) has been suggested to play an important role in cell migration which is critical for tumor metastasis. Here we investigated the role of P-Rex1, a novel specific GEF for Rac, in human prostate cancer cell migration. PCR and immunofluorescent staining showed that the expression of P-Rex1 was undetectable in normal prostate epithelial cells (PrEC) and less metastatic LNCaP cells but significantly increased in more metastatic prostate cancer cell lines (DU-145, PC-3-LN4 and PC-3). Our study also revealed increased P-Rex1 protein level in human prostate tumor specimens compared to the corresponding normal prostate tissues. Using an in vitro transwell migration chamber assay, we found that NIH-3T3 conditioned media (3T3-CM) can induce prostate cancer cell migration which positively correlates with expression levels of P-Rex1. Exogenously expressed P-Rex1 enhanced Gi-coupled receptor-dependent migration of PC-3-LN4 cells up to four-fold in a dose-dependent manner. Knockdown of endogenous P-Rex1 by small interfering RNA reduced the migration of PC-3 cells. Furthermore, exogenous expression of P-Rex1 in PC-3-LN4 cells induced strong Rac-dependent lamellipodia. Our results suggest that up-regulation of P-Rex1 promotes prostate cancer cell migration and contributes to the metastasis of prostate cancer. (The Nebraska State LB595 to Y. Tu.)