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Title: | P21-activated kinase 1 promotes colorectal cancer survival by up-regulation of hypoxia-inducible factor-1α. | Austin Authors: | Liu, Kevin H;Huynh, Nhi;Patel, Oneel;Shulkes, Arthur;Baldwin, Graham S;He, Hong | Affiliation: | Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia | Issue Date: | 26-Jun-2013 | Publication information: | Cancer Letters 2013; 340(1): 22-9 | 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. | Gov't Doc #: | 23811286 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/11803 | DOI: | 10.1016/j.canlet.2013.06.024 | Journal: | Cancer letters | URL: | https://pubmed.ncbi.nlm.nih.gov/23811286 | Type: | Journal Article | Subjects: | CRC HIF-1α PAK1 β-Catenin Animals Cell Hypoxia Cell Survival Colorectal Neoplasms.enzymology.pathology.therapy Enzyme Activation Female Gene Expression Regulation, Neoplastic Gene Knockdown Techniques HCT116 Cells HT29 Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit.genetics.metabolism Male Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID RNA, Small Interfering.genetics Tumor Burden Up-Regulation Vascular Endothelial Growth Factor A.secretion beta Catenin.metabolism p21-Activated Kinases.antagonists & inhibitors.physiology |
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