Abstract
P21 activated kinase 1 (PAK1) enhances colorectal cancer (CRC) progression by stimulating Wnt/β-catenin and Ras oncogene, which promote CRC survival via stimulation of hypoxia-inducible factor 1α (HIF-1α). The aim of this study was to assess the mechanism involved in the stimulation by PAK1 of CRC survival. PAK1 promoted CRC cell survival by up-regulation of HIF-1α. PAK1 was over-expressed and hyper-activated in tumors of ApcΔ(14/+) mice, which was correlated with over-expression of HIF-1α and β-catenin. Inhibition of PAK1 decreased tumor growth and the expression of HIF-1α and β-catenin in tumors of ApcΔ(14/+) mice, and suppressed xenograft tumor survival in SCID mice. These findings indicate that PAK1 stimulates CRC survival by up-regulation of HIF-1α.
Keywords:
CRC; HIF-1α; PAK1; β-Catenin.
Copyright © 2013 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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Cell Hypoxia
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Cell Survival
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Colorectal Neoplasms / enzymology*
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / therapy
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Enzyme Activation
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Female
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Gene Expression Regulation, Neoplastic
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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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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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RNA, Small Interfering / genetics
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Tumor Burden
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Up-Regulation
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Vascular Endothelial Growth Factor A / metabolism
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beta Catenin / metabolism
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p21-Activated Kinases / antagonists & inhibitors
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p21-Activated Kinases / physiology*
Substances
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CTNNB1 protein, human
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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RNA, Small Interfering
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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beta Catenin
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PAK1 protein, human
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p21-Activated Kinases