YAP 信号通路参与 WDR1 调控的非小细胞肺癌细胞的增殖和迁移。
YAP signaling is involved in WDR1-regulated proliferation and migration of non-small-cell lung cancer cells.
机构信息
Biomedical Research Institute, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430081, P.R. China.
Central Laboratory, Nanjing Chest Hospital, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, Nanjing 210029, P. R. China.
出版信息
Exp Biol Med (Maywood). 2022 Sep;247(18):1619-1629. doi: 10.1177/15353702221110645. Epub 2022 Jul 21.
As a major co-factor of F-actin depolymerization, WD-repeat domain 1 (WDR1) affects the cellular microenvironment by cytoskeleton remodeling, thereby influencing cell molecular behavior. Our previous study showed that WDR1 activates YAP (Yes-associated protein) signaling in non-small-cell lung cancer (NSCLC) cells, but the mechanism remains unclear. We discovered that knockdown WDR1 in NSCLC cells decreased the expression of YAP and the nucleus-to-cytoplasm ratio. Disruption of cortical stress by drugs significantly inhibited YAP nuclear trafficking and enhanced YAP phosphorylation. In WDR1-knockdown NSCLC cells, inhibition of Hippo pathway reduced the nuclear exclusion of YAP and phosphorylated YAP. Our data suggest that WDR1-mediated cortical stress might be involved in regulating YAP signaling, thereby affecting the proliferation and migration of NSCLC cells.
作为 F-肌动蛋白解聚的主要辅助因子，WD 重复结构域 1（WDR1）通过细胞骨架重塑影响细胞微环境，从而影响细胞分子行为。我们之前的研究表明，WDR1 在非小细胞肺癌（NSCLC）细胞中激活 YAP（Yes 相关蛋白）信号通路，但机制尚不清楚。我们发现，敲低 NSCLC 细胞中的 WDR1 会降低 YAP 的表达和核质比。药物破坏皮质应激显著抑制 YAP 核易位并增强 YAP 磷酸化。在 WDR1 敲低的 NSCLC 细胞中，抑制 Hippo 通路减少了 YAP 的核排斥和磷酸化 YAP。我们的数据表明，WDR1 介导的皮质应激可能参与调节 YAP 信号通路，从而影响 NSCLC 细胞的增殖和迁移。
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