癌症研究
癌细胞
细胞生长
激酶
化学
丝状体
生物
蛋白激酶A
细胞生物学
癌症
生物化学
肌动蛋白
遗传学
作者
Jian Zhang,Jian Wang,Qiqiang Guo,Yu Wang,Zhe Ying,Hong-lin Peng,Dongmei Zhao,Feng Li
出处
期刊:Cancer Letters
[Elsevier]
日期:2012-04-01
卷期号:317 (1): 24-32
被引量:88
标识
DOI:10.1016/j.canlet.2011.11.007
摘要
P21-activated kinase 4 (PAK4), a serine/threonine protein kinase, has involved in the regulation of cytoskeletal reorganization, cell proliferation, gene transcription, oncogenic transformation and cell invasion. Moreover, PAK4 overexpression, genetic amplification and mutations were detected in a variety of human tumors, which make it potential therapeutic target. In this paper we found that LCH-7749944, a novel and potent PAK4 inhibitor, effectively suppressed the proliferation of human gastric cancer cells through downregulation of PAK4/c-Src/EGFR/cyclin D1 pathway. In addition, LCH-7749944 significantly inhibited the migration and invasion of human gastric cancer cells in conjunction with concomitant blockage of PAK4/LIMK1/cofilin and PAK4/MEK-1/ERK1/2/MMP2 pathways. Interestingly, LCH-7749944 also inhibited the formation of filopodia and induced cell elongation in SGC7901 cells. Importantly, LCH-7749944 caused successful inhibition of EGFR activity due to its inhibitory effect on PAK4. Taken together, these results provided novel insights into the development of PAK4 inhibitor and potential therapeutic strategies for gastric cancer.
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