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.
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
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Cell Proliferation*
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Colorectal Neoplasms / enzymology*
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Colorectal Neoplasms / genetics
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Colorectal Neoplasms / pathology
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Gene Knockdown Techniques*
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HCT116 Cells
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HT29 Cells
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Humans
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Liver Neoplasms / enzymology
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Liver Neoplasms / genetics
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Liver Neoplasms / secondary
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Mice
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Mice, SCID
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Neoplasm Invasiveness
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Proto-Oncogene Proteins c-myc / metabolism
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RNA Interference
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Signal Transduction
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Time Factors
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Transcription Factor 4
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Transcription Factors / metabolism
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Transfection
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Tumor Burden
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Xenograft Model Antitumor Assays
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beta Catenin / genetics
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beta Catenin / metabolism*
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p21-Activated Kinases / deficiency*
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p21-Activated Kinases / genetics
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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CTNNB1 protein, human
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MYC protein, human
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Proto-Oncogene Proteins c-myc
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin
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PAK1 protein, human
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p21-Activated Kinases