Journal
AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH
Volume 9, Issue 6, Pages 2736-2747Publisher
E-CENTURY PUBLISHING CORP
Keywords
LC-0882; small molecular compound; PAK4; gastric cancer
Categories
Funding
- National Natural Science Foundation of China [81302127, 81230077, 31371424, 31571457]
- Specialized Research Fund for the Doctoral Program of Higher Education in China [20132104120018]
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Gastric cancer is the most common malignant tumor and globally the third leading cause of cancer-related deaths. Therefore, there exists an urgent need to identify new effective gastric cancer treatments. Given the important roles in tumorigenesis and progression, p21-activated kinase 4 (PAK4) has been regarded as an attractive high-value druggable target. In this study, we examined the effects and molecular mechanisms of action of the small molecular compound LC-0882 on gastric cancer cells in vitro. LC-0882 was found to significantly inhibit the proliferation of human gastric cancer cells by repressing phospho-PAK4/cyclin D1 and CDK4/6 expression. In addition, LC-0882 was found to attenuate cell invasion by blocking the PAK4/LIMK1/cofilin signaling pathway. Finally, analysis of immunofluorescence revealed that LC-0882 exposure decreased filopodia formation and induced cell elongation in BGC823 and SGC7901 gastric cancer cells. These findings suggest that targeting PAK4 with the novel compound LC-0882 may provide a new chemotherapeutic approach in gastric cancer treatment.
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