KPT-9274 shows specificity for attenuation of PAK4 targets preferentially in RCC cells. KPT-9274 shows specificity for attenuation of PAK4 targets preferentially.

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KPT-9274 shows specificity for attenuation of PAK4 targets preferentially in RCC cells. KPT-9274 shows specificity for attenuation of PAK4 targets preferentially in RCC cells. Both RCC cell lines in addition to a normal primary renal proximal tubular epithelial cell line (RPTEC) were grown to 50% and transfected with an siRNA specific to PAK4 or a scrambled sequence control siRNA, then subjected to immunoblotting (A) and apoptosis assay by flow cytometry (B). C, whole cell lysates were immunoblotted with the indicated antibodies after incubation of the cells with the indicated concentrations of KPT-9274. D, the subcellular localization of β-catenin in 786-O cells was determined by immunofluorescent staining after 24 hours of treatment with DMSO, 1 μmol/L or 5 μmol/L KPT-9274. The fluorescence of FITC-conjugated β-catenin (green), TRITC-conjugated phalloidin (F-actin stained: red), and DAPI (nucleus counter-stained: blue) was visualized under a confocal laser-scanning microscope. Scale bar, 20 μm. E, Western blot analysis of β-catenin in the cytosolic and nuclear portions of 786-O cells exposed to DMSO or KPT-9274 for 36 and 72 hours. TBP, TATA-binding protein, a nuclear constituent. For details, see Materials and Methods. Omran Abu Aboud et al. Mol Cancer Ther 2016;15:2119-2129 ©2016 by American Association for Cancer Research