Int. J. Mol. Sci. 2016, 17(4), 470; https://doi.org/10.3390/ijms17040470
GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways
1
Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China
2
Key Laboratory of Structure-Based Drug Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China
*
Author to whom correspondence should be addressed.
Academic Editor: Ge Zhang
Received: 14 February 2016 / Revised: 12 March 2016 / Accepted: 24 March 2016 / Published: 11 April 2016
(This article belongs to the Special Issue Translational Molecular Medicine & Molecular Drug Discovery)
Abstract
Gastric cancer, which is the most common malignant gastrointestinal tumor, has jumped to the third leading cause of cancer-related mortality worldwide. It is of great importance to identify novel and potent drugs for gastric cancer treatment. P21-activated kinase 4 (PAK4) has emerged as an attractive target for the development of anticancer drugs in consideration of its vital functions in tumorigenesis and progression. In this paper, we reported that GL-1196, as a small molecular compound, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclinD1 pathway and CDK4/6 expression. Moreover, GL-1196 prominently inhibited the invasion of human gastric cancer cells in parallel with blockage of the PAK4/LIMK1/cofilin pathway. Interestingly, GL-1196 also inhibited the formation of filopodia and induced cell elongation in SGC7901 and BGC823 cells. Taken together, these results provided novel insights into the potential therapeutic strategy for gastric cancer. View Full-TextKeywords:
GL-1196; PAK4; small molecular compound; gastric cancer
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Zhang, J.; Zhang, H.-Y.; Wang, J.; You, L.-H.; Zhou, R.-Z.; Zhao, D.-M.; Cheng, M.-S.; Li, F. GL-1196 Suppresses the Proliferation and Invasion of Gastric Cancer Cells via Targeting PAK4 and Inhibiting PAK4-Mediated Signaling Pathways. Int. J. Mol. Sci. 2016, 17, 470.
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