P21-activated kinase 1 promotes colorectal cancer survival by up-regulation of hypoxia-inducible factor-1α.

Cancer Lett 2013 Oct 26;340(1):22-9. Epub 2013 Jun 26.

Department of Surgery, University of Melbourne, Austin Health, Heidelberg, Victoria 3084, Australia.

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.

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http://dx.doi.org/10.1016/j.canlet.2013.06.024DOI Listing
October 2013

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