Department of Pediatrics, University of Illinois at Chicago, Chicago, IL 60612, USA.
FEBS Lett. 2012 May 21;586(10):1510-5. doi: 10.1016/j.febslet.2012.04.009. Epub 2012 Apr 20.
Although von Hippel-Lindau protein (pVHL) is known as a tumor suppressor in kidney and other organs, it remains unclear whether pVHL plays a role in lung cancer development. We investigated the role of pVHL in lung cancer cell proliferation, migration, and colonization using stable A549 cells with knockdown of pVHL. We found that knockdown of pVHL promotes epithelial-mesenchymal transition (EMT) in lung cancer cells. Knockdown of pVHL decreased tumor colonization in a tail-vein injection model and decreased cell proliferation, whereas overexpression of constitutive active HIF increased tumor colonization, suggesting a HIF-independent function of pVHL in lung. Knockdown of pVHL decreased phosphorylation of FAK and expression of integrin, suggesting that pVHL regulates lung cancer development via integrin/FAK signaling pathway.
尽管 von Hippel-Lindau 蛋白 (pVHL) 被认为是肾脏和其他器官中的肿瘤抑制因子，但它在肺癌发展中的作用仍不清楚。我们使用稳定的 A549 细胞，通过敲低 pVHL，研究了 pVHL 在肺癌细胞增殖、迁移和定植中的作用。我们发现，敲低 pVHL 促进了肺癌细胞的上皮-间充质转化（EMT）。pVHL 的敲低降低了尾静脉注射模型中的肿瘤定植，降低了细胞增殖，而组成型激活 HIF 的过表达增加了肿瘤定植，这表明 pVHL 在肺中具有 HIF 独立的功能。pVHL 的敲低降低了 FAK 的磷酸化和整合素的表达，这表明 pVHL 通过整合素/FAK 信号通路调节肺癌的发生。
