Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway

Abstract

PAK5 (p21 activated kinase 5) is upregulated in human colorectal carcinoma cells and is a known tumor promoter in carcinogenesis of the colon. Little is known regarding the mechanisms underlying the downstream targets of PAK5, and information concerning its biological significance in glioma is lacking. In this study, we investigated the effects of PAK5 on proliferation, migration, invasion, and apoptosis in human U87 and U251 glioma cells and examined the underlying molecular mechanism. We performed cell growth assays and cell cycle analysis to observe the cell proliferation. Flow cytometry analysis was performed to evaluate apoptosis, and in vitro scratch assays, cell migration assays, and gelatin zymography were performed to examine cell migration. Western blot analysis was performed to examine signal transduction in the cells. We demonstrated that suppression of PAK5 in glioma cells significantly inhibited cell migration and invasion. We also observed that suppression of PAK5 in human glioma cell lines inhibited cell growth because of G1 phase arrest. Additionally, flow cytometry and Western blot analysis indicated that PAK5 could inhibit cell apoptosis. These results suggest that the PAK5-Egr1-MMP2 signaling pathway is involved in tumor progression and may have a potential role in cancer prevention and treatment.

Retraction: ‘p53‐induced Rap2B positively regulates migration in cells exposed to glucose deprivation’ by D.‐S. Pei, J.‐H. Di, W.‐Q. Du and J.‐N. Zheng

“…Migration assay was performed as described previously [15]. In brief, cell migration was determined by using a modified two chamber migration assay with a pore size of 8 mm.…”

p21-Activated kinase 5 affects cisplatin-induced apoptosis and proliferation in hepatocellular carcinoma cells

“…Past studies have reported that PAK5 played a critical role in cytoskeleton regulation, which could impact cancer cell motility and angiogenesis, thereby causing invasion and distant metastasis [7][8][9]. It was reported that the PAK5-Egr1-MMP2 signal pathway could also affect tumor invasion and migration [7]. Moreover, studies have shown that overexpression of PAK5 decreased apoptosis and promoted cell survival through phosphorylating BAD on serine 112, and indirectly phosphorylating serine 136 via the activation of the Akt pathway [10][11][12].…”

“…PAK5 contained a highly conserved p21-GTPase-binding domain (PBD) and shared over 80 % sequence identities in the kinase domain, which was characteristic of other members of the group II PAK family [4,6]. Past studies have reported that PAK5 played a critical role in cytoskeleton regulation, which could impact cancer cell motility and angiogenesis, thereby causing invasion and distant metastasis [7][8][9]. It was reported that the PAK5-Egr1-MMP2 signal pathway could also affect tumor invasion and migration [7].…”

miR-129 suppresses tumor cell growth and invasion by targeting PAK5 in hepatocellular carcinoma

“…PAK5 regulates MMP-2 in the mediation of tumor invasion and metastasis in glioma cells [13]. But its role in hepatocellular carcinoma needs to be further revealed, although several reports indicated that PAK5 involved in enhanced proliferation and tumorigenicity [14].…”