ABSTRACT

Krüppel-like factor 5 (KLF5) can both promote and suppress cell migration, but the underlying mechanisms have not been elucidated. In this study, we show that the function of KLF5 in epithelial-mesenchymal transition (EMT) and migration of liver cancer cells depends on the status of the cellular tumor antigen p53 (p53). Furthermore, zinc finger E-box-binding homeobox 2 (ZEB2) is the main regulator of KLF5 in EMT in liver cancer cells in the context of p53 loss. Most importantly, the regulation of ZEB2 by p53 and KLF5 is indirect and that miR-192 mediates this regulation. Finally, we find that in invasive liver cancer, KLF5 is absent in the context of p53 loss or mutation.

摘要

Krüppel 样因子 5 (KLF5) 可以促进和抑制细胞迁移，但其潜在机制尚未阐明。在这项研究中，我们表明 KLF5 在上皮间质转化 (EMT) 和肝癌细胞迁移中的功能取决于细胞肿瘤抗原 p53 (p53) 的状态。此外，锌指 E-box 结合同源框 2 (ZEB2) 是在 p53 丢失的情况下肝癌细胞 EMT 中 KLF5 的主要调节因子。最重要的是，p53 和 KLF5 对 ZEB2 的调节是间接的，而 miR-192 介导了这种调节。最后，我们发现在浸润性肝癌中，在 p53 丢失或突变的情况下，KLF5 不存在。