Overexpression of p21-activated kinase 1 promotes endometrial cancer progression.

Endometrial cancer (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. P21-activated kinase 1 (Pak1) plays important roles in cell motility and survival. This study investigated the clinical significance of Pak1 expression and its functional roles in EC. The expression of Pak1 in clinical samples and EC cell lines was evaluated. The effects of Pak1 on EC cell functions were determined by either overexpressing it via plasmid transfection or depleting its expression using short hairpin RNA (shRNA) in human EC cell lines. Pak1 was overexpressed in clinical samples of EC compared with normal endometrium. High Pak1 expression in EC was positively correlated with lymph node metastasis, advanced disease stage and poor histological differentiation. Pak1 over-expression was also observed in multiple human EC cell lines. In EC cell lines, Pak1 overexpression promoted cell proliferation, migration, invasion and anchorage-independent growth in vitro. Conversely, shRNA-mediated stable knockdown of Pak1 reduced cell proliferation, migration, invasion and anchorage-independent growth. In addition, ectopic Pak1 overexpression protected EC cells from apoptosis, along with decreased caspase-3 activation. These results suggest that Pak1 plays important roles at multiple stages of EC progression.