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PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell

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Tumor Biology

Abstract

p21-activated kinases (PAKs) are activated by various extracellular stimuli and, in turn, activate other kinases by phosphorylating them at specific serine/threonine residues or through protein–protein interaction. As a recently identified member of the group B PAK family, the role of PAK5 in cancer is poorly understood. In this study, we investigated the effect of PAK5 on the malignant phenotype, such as proliferation, cell cycle, apoptosis, migration, and invasion. Cell growth assay and cell cycle analysis consistently showed that knockdown of PAK5 could significantly inhibit the proliferation of breast cancer cells. Wound healing assay. migration assay, and invasion assay showed that PAK5 promoted cell migration. Furthermore, in order to elucidate the underlying mechanism of PAK5 on cellular growth and migration, we examined the protein expressions of cyclin D1, p21, early growth response protein 1 (Egr1), and matrix metalloproteinase 2 (MMP2). Our work further reveals the PAK5-Egr1-MMP2 signaling pathway to be a critical regulator of cell migration and invasion. These results suggest that PAK5 may be a potential therapeutic target for breast cancer.

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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).

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Authors and Affiliations

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

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

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

    Jun-Nian Zheng

Authors
  1. Xiao-Xia Wang
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  2. Qian Cheng
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  3. Shang-Nuan Zhang
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  4. He-ya Qian
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  5. Jin-Xia Wu
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  6. Hui Tian
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  7. Dong-Sheng Pei
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Corresponding authors

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

Additional information

Xiao-Xia Wang, Qian Cheng, and Shang-Nuan Zhang contributed equally to this paper.

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Wang, XX., Cheng, Q., Zhang, SN. et al. PAK5-Egr1-MMP2 signaling controls the migration and invasion in breast cancer cell. Tumor Biol. 34, 2721–2729 (2013). https://doi.org/10.1007/s13277-013-0824-x

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  • DOI: https://doi.org/10.1007/s13277-013-0824-x

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