Gastric cancer is one of the most common neoplasms in digestive system with highly malignant and a poor prognosis worldwide, especially in Asia and Africa
. It tends to be associated with lymph node metastasis, peritoneal dissemination, and hematogenous metastasis. Despite the advancement of surgical technique and the improvement of anticancer drugs in recent years, gastric cancer is still a leading cause of cancer-related deaths and the 5-year survival rate is approximately 20%
. Especially in China, the morbidity of gastric cancer has reached to second with 3,621,000 new cases, whilst the mortality rate ranked third with the proportion of 14.33% annually
. It has been demonstrated that the depth of tumor invasion, peritoneal dissemination, hepatic metastasis, and lymph node metastasis are significant factors in determining prognosis
. Since tumor invasion and metastasis are very complicated and continuous processes involving multiple steps, regulated at the molecular level by adhesion molecules, protein catabolic enzymes, cellular growth factors, and various angiogenic factors, it is extremely necessary to identify novel and efficient biomarkers for the evaluation of the behavior in tumor development and metastasis in order to predict prognosis and improve therapeutic strategies for patients with gastric cancer.
The p21-activated kinases (PAKs) are a family of serine/threonine protein kinases, which were initially identified as binding partners of the Rho GTPases Cdc42 and Rac1
. The PAK family includes six isoforms (PAK1-6) which play a crucial role in a variety of physiological processes such as motility, survival, mitosis, apoptosis, and hormone signaling
. The PAKs are divided into two groups, group I (PAKs 1–3) and group II (PAKs 4–6) based on structural and functional similarities: group I PAKs exist in an inactive homodimer maintained by interactions between the autoinhibitory domain (AID) and kinase domain of PAK monomers; group II PAKs also bind Rac and Cdc42, but they lack an AID, exist as active monomers, and have not been reported to have a scaffolding function
. Recent studies have demonstrated that PAKs are overexpressed, hyperactivated or amplified in several human cancers and their role in cell transformation make them attractive therapeutic targets
. Especially, PAK2, which has an overall 76% homology with PAK1 and 96% homology in the kinase domain, has a dual role in both cell survival and cell death pathways. It is widely distributed throughout the body and is not only activated by binding with the small G protein complex Cdc42/Rac, but it is also cleaved and activated by caspase-3 and similar proteases
. Full length PAK2 is autophosphorylated at eight sites including Ser20, Ser139, Ser141, Ser144, Ser192, Thr402, Thr421 and Thr423, and then activated
. Accumulating evidence indicates that PAK2 are either up-regulated or hyperactivated in a variety of human cancers, including ovarian cancer
 and breast cancer
. PAK2 plays an important role in tumor aggressiveness, but its involvement in gastric cancer has not yet clear. The aim of this study was to investigate whether PAK2 expression and its phosphorylation status are correlated with tumor progression and prognosis in gastric cancer.