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

• DOI: 10.3892/or.2017.5643
• Publication Date: 2017-05-16T08:44:15Z
• Authors: Liang-Hui Li; Guo-Yang Wu; Yi-Zhuo Lu; Xue-Hua Chen; Bing-Ya Liu; Min-Hua Zheng; Jian-Chun Cai
• Keywords: Male; 0303 health sciences; JNK Mitogen-Activated Protein Kinases; Apoptosis; Middle Aged; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; p21-Activated Kinases; Cell Movement; Stomach Neoplasms; Lymphatic Metastasis; Tumor Cells, Cultured; Humans; Matrix Metalloproteinase 2; Female; Neoplasm Invasiveness; Cell Proliferation

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.