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

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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.

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Acknowledgments

This project is supported by grants from the key project of the Education Department of China (212062) and the Program for New Century Excellent Talents in University (NCET-08-0700).

Conflict of interest

We declare that we have no conflict of interest.

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Authors and Affiliations

  1. Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People’s Republic of China

    Xiao-Xia Wang, Shang-Nuan Zhang, Jin-Xia Wu, He-ya Qian, Yi-yang Wen, Hui Tian, Dong-Sheng Pei & Jun-Nian Zheng

  2. Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, 221002, China

    Zheng-Xiang Han & Jun-Nian Zheng

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  1. Zheng-Xiang Han
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  2. Xiao-Xia Wang
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  7. Hui Tian
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Corresponding authors

Correspondence to Dong-Sheng Pei or Jun-Nian Zheng.

Additional information

Z.-X. Han and X.-X. Wang contributed equally to this article.

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Han, ZX., Wang, XX., Zhang, SN. et al. Downregulation of PAK5 inhibits glioma cell migration and invasion potentially through the PAK5-Egr1-MMP2 signaling pathway. Brain Tumor Pathol 31, 234–241 (2014). https://doi.org/10.1007/s10014-013-0161-1

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  • DOI: https://doi.org/10.1007/s10014-013-0161-1

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