Journal article
P-21 activated kinase 1 knockdown inhibits β-catenin signalling and blocks colorectal cancer growth
H He, N Huynh, KH Liu, C Malcontenti-Wilson, J Zhu, C Christophi, A Shulkes, GS Baldwin
Cancer Letters | Published : 2012
Abstract
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 β-catenin expression, β-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. © 2011 Elsevier Ireland Ltd.
Grants
Awarded by National Health and Medical Research Council
Funding Acknowledgements
We thank Ms. Linh Nguyen for her assistance with the mouse liver metastasis model, and Dr. Suzana Kovac and Dr. Kathryn Marshall for helpful discussions. This work was supported by National Health and Medical Research Council of Australia Grant 508908 to HH.