Recent studies revealed that the histone demethylase KDM2B regulates the epithelial markers E-Cadherin and ZO-1, the RhoA/B/C-small-GTPases and actin cytoskeleton organization, in DU-145 prostate- and HCT-116 colon-tumor cells. Here we addressed the role of KDM2B in the activation of Focal Adhesion Kinase (FAK)-signaling and its involvement in regulating tumor cell motility. We used RT-PCR for gene transcriptional analysis, Western blotting for the assessment of protein expression and activity and wound-healing assay for the study of cell migration. KDM2B overexpression or silencing controls the activity of FAK in DU-145 prostate- and HCT-116 colon-tumor cells without affecting gene transcription and protein expression of this kinase. Upon KDM2B overexpression in DU-145 cells, significantly enhanced migration was observed, which was abolished in cells pretreated by the specific phosphoinositide-3 kinase (PI3 K) inhibitor LY294002, implying involvement of FAK/PI3 K signaling in the migration process. In line with this, the p85-PI3 K-subunit was downregulated upon knockdown of KDM2B in DU-145 cells, while the opposite effect became evident in KDM2B-overexpressing cells. These results revealed a novel functional role of KDM2B in regulating the activation of the FAK/PI3 K signaling in prostate cancer cells that participates in the control of cell motility.

最近的研究表明，组蛋白脱甲基酶KDM2B在DU-145前列腺癌和HCT-116结肠癌细胞中调节上皮标记E-钙黏着蛋白和ZO-1，RhoA / B / C-小GTP酶和肌动蛋白细胞骨架组织。在这里，我们解决了KDM2B在局灶性粘附激酶（FAK）信号激活及其在调节肿瘤细胞运动性中的作用。我们使用RT-PCR进行基因转录分析，使用蛋白质印迹法评估蛋白质表达和活性，并使用伤口愈合分析法研究细胞迁移。KDM2B过表达或沉默控制DU-145前列腺和HCT-116结肠肿瘤细胞中FAK的活性，而不会影响该激酶的基因转录和蛋白质表达。在DU-145细胞中KDM2B过表达后，观察到迁移明显增强，在经过特定的磷酸肌醇3激酶（PI3 K）抑制剂LY294002预处理的细胞中，这被消除，这意味着FAK / PI3 K信号传导参与了迁移过程。与此相符的是，在敲除DU-145细胞中的KDM2B后，p85-PI3 K亚基被下调，而在过表达KDM2B的细胞中相反的作用变得明显。这些结果揭示了KDM2B在调节参与细胞运动控制的前列腺癌细胞中FAK / PI3K信号传导的激活中的新功能作用。而相反的效果在过表达KDM2B的细胞中变得明显。这些结果揭示了KDM2B在调节参与细胞运动控制的前列腺癌细胞中FAK / PI3K信号传导的激活中的新功能作用。而相反的效果在过表达KDM2B的细胞中变得明显。这些结果揭示了KDM2B在调节参与细胞运动性控制的前列腺癌细胞中FAK / PI3K信号传导的激活中的新功能作用。