P21 activated kinase 2 promotes pancreatic cancer growth and metastasis.

Abstract

Pancreatic cancer has an overall 5-year survival rate of only 9%, due to its rapid metastasis and poor prognosis. To combat this disease, novel therapeutic targets and biomarkers are required. In this study, immunohistochemistry was used to detect the expression of P21 activated kinase 2 (PAK2) protein in the tissues of cancer and the paired adjacent normal tissues. The association between PAK2 and the clinicopathologic features of patients with pancreatic cancer was subsequently analyzed. The results indicated that PAK2 was overexpressed in the cancer tissues, which indicated high pTNM stage, poor tumor grade, lymph node metastasis and vascular invasion. In addition, the results demonstrated evidence of a close association between PAK2 expression and poor prognosis of patients with pancreatic cancer. The results also suggested that PAK2 may promote pancreatic cancer cell proliferation and migration in vitro through clone formation, MTT, wound healing and Transwell assays. The present study further identified that PAK2 could stimulate pancreatic cancer growth and metastasis in mice. Decreased expression of proliferation marker protein Ki-67 and proliferating cell nuclear antigen in response to PAK2 knockdown further verified the role of PAK2 in promoting cell proliferation by western blot analysis. In addition, the expression levels of matrix metallopeptidase (MMP) 2 and MMP9 were decreased in PANC1 and BxPC3 cell lines transfected with PAK2-short hairpin RNA as indicated in western blot analysis, suggesting a function of PAK2 in promoting cell invasion. Collectively, these findings revealed a critical role for PAK2 in the development of pancreatic cancer and may have important implications for the management of this disease.