LC-0882 Targets PAK4 and Inhibits PAK4-related Signaling Pathways to Suppress the Proliferation and Invasion of Gastric Cancer Cells

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2017 Jul 4

PMID 28670365

Citations 10

Authors

Hong-Yan Zhang

Jian Zhang

Chen-Zhou Hao

Ying Zhou

Jian Wang

Mao-Sheng Cheng

Dong-Mei Zhao

Feng Li

Affiliations

Soon will be listed here.

Abstract

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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