Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway.
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.
Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China.
Zheng-Xiang
ZX
Han
Xiao-Xia
XX
Wang
Shang-Nuan
SN
Zhang
Jin-Xia
JX
Wu
He-ya
HY
Qian
Yi-yang
YY
Wen
Hui
H
Tian
Dong-Sheng
DS
Pei
Jun-Nian
JN
Zheng
D017209:Apoptosis / Q000235:genetics*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology*; D002453:Cell Cycle / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics*; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005910:Glioma / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000502:physiology*; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases / Q000235:genetics* / Q000502:physiology*
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C443802:PAK5 protein, human; D054462:p21-Activated Kinases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2