P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth
P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth
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DOI：
10.1016/j.canlet.2011.11.014
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发表时间：
2012-04-01
期刊：
影响因子：
9.7
通讯作者：
Baldwin, Graham S.
中科院分区：
文献类型：
--
作者：
He, Hong;Nhi Huynh;Baldwin, Graham S.
p21激活激酶1（PAK 1）在细胞生长、运动和转化中起重要作用。本研究的目的是阐明PAK 1下游的信号传导机制，并研究PAK 1对结直肠癌（CRC）生长和转移的重要性。在人CRC细胞系中PAK 1敲低抑制β-连环蛋白表达、β-连环蛋白/TCF 4转录活性和c-Myc表达。在小鼠模型中，PAK 1敲低通过减少增殖和增加凋亡来抑制人CRC细胞的生长和转移。我们的研究结果首次证明了PAK 1在体内CRC进展中的关键作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The p21-activated kinase 1 (PAK1) plays important roles in cell growth, motility, and transformation. The aims of this study were to delineate the signalling mechanisms downstream of PAK1, and to investigate the importance of PAK1 for colorectal cancer (CRC) growth and metastasis in vivo. PAK1 knockdown in human CRC cell lines inhibited beta-catenin expression, beta-catenin/TCF4 transcriptional activity, and the expression of c-Myc. In mouse models PAK1 knockdown suppressed the growth and metastasis of human CRC cells by decreasing proliferation and increasing apoptosis. Our findings demonstrate for the first time the crucial role of PAK1 in CRC progression in vivo. (C) 2011 Elsevier Ireland Ltd. All rights reserved.