p21-activated protein kinase 1 induces the invasion of gastric cancer cells through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase-2

  • Authors:
    • Liang-Hui Li
    • Guo-Yang Wu
    • Yi-Zhuo Lu
    • Xue-Hua Chen
    • Bing‑Ya Liu
    • Min-Hua Zheng
    • Jian-Chun Cai
  • View Affiliations

  • Published online on: May 16, 2017     https://doi.org/10.3892/or.2017.5643
  • Pages: 193-200
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Abstract

Gastric cancer (GC) is one of the most common malignancies worldwide. The prognosis of GC is poor, mostly due to widespread metastasis. p21-activated kinase 1 (Pak1), the best characterized member of an evolutionarily conserved family of serine/threonine kinases, plays an important role in the regulation of cell morphogenesis, motility, mitosis and angiogenesis. By qRT-PCR and Gelatin zymograph assay, we demonstrated in the present study that stable overexpression of Pak1 induced matrix metalloproteinase (MMP)-2 mRNA expression and activity in the human MKN45 GC cell line. Conversely, knockdown of endogenous Pak1 expression by small interfering RNA (siRNA) decreased MMP-2 mRNA expression and activity in the MKN45 GC cells. Activation of c-Jun N-terminal kinase (JNK) was required for Pak1-induced upregulation of MMP-2 mRNA level and activity. Moreover, upregulation of MMP-2 by Pak1 via the JNK pathway notably promoted the invasion of MKN45 GC cells. Overexpression of MMP-2 mRNA was once again confirmed to be associated with GC metastasis. In conclusion, our results demonstrated for the first time that Pak1 stimulated MMP-2 mRNA expression and activity in MKN45 GC cells. The JNK signaling pathway was involved in Pak1 modulation of MMP-2, which was important for MKN45 GC cell invasiveness.
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July-2017
Volume 38 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Li L, Wu G, Lu Y, Chen X, Liu BY, Zheng M and Cai J: p21-activated protein kinase 1 induces the invasion of gastric cancer cells through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase-2. Oncol Rep 38: 193-200, 2017
APA
Li, L., Wu, G., Lu, Y., Chen, X., Liu, B., Zheng, M., & Cai, J. (2017). p21-activated protein kinase 1 induces the invasion of gastric cancer cells through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase-2. Oncology Reports, 38, 193-200. https://doi.org/10.3892/or.2017.5643
MLA
Li, L., Wu, G., Lu, Y., Chen, X., Liu, B., Zheng, M., Cai, J."p21-activated protein kinase 1 induces the invasion of gastric cancer cells through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase-2". Oncology Reports 38.1 (2017): 193-200.
Chicago
Li, L., Wu, G., Lu, Y., Chen, X., Liu, B., Zheng, M., Cai, J."p21-activated protein kinase 1 induces the invasion of gastric cancer cells through c-Jun NH2-terminal kinase-mediated activation of matrix metalloproteinase-2". Oncology Reports 38, no. 1 (2017): 193-200. https://doi.org/10.3892/or.2017.5643