文章：

FBXO11介导ZEB1泛素化并调控肺癌细胞上皮-间质转化过程

FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells

原文发布日期：26 September 2024

DOI: 10.3390/cancers16193269

类型: Article

开放获取: 是

英文摘要：

Epithelial-to-mesenchymal transition (EMT) affects the invasion and migration of cancer cells. Here, we show that FBXO11 recognizes and promotes ubiquitin-mediated degradation of ZEB1. There is a strong association between FBXO11 and ZEB1 in non-small cell lung cancer (NSLC) in a clinical database. FBXO11 interacts with ZEB1, a core inducer of EMT. FBXO11 leads to increased ubiquitination and proteasomal degradation of ZEB1. Depletion of endogenous FBXO11 causes ZEB1 protein accumulation and EMT in A549 and H1299 cells, while overexpression of FBXO11 reduces ZEB1 protein abundance and cellular invasiveness. Importantly, the depletion of ZEB1 suppresses the increased migration and invasion of A549 and H1299 cells promoted by the depletion of FBXO11. The same results are shown in xenograft tumors. High FBXO11 expression is associated with a favorable prognosis in NSLC. Collectively, our study demonstrates that FBXO11 modulates EMT by mediating the stability of ZEB1 in lung cancer cells.

摘要翻译： 

上皮-间质转化（EMT）影响癌细胞的侵袭和迁移能力。本研究发现FBXO11能够识别并促进ZEB1的泛素化降解。临床数据库分析显示，在非小细胞肺癌（NSLC）中FBXO11与ZEB1存在显著关联。FBXO11可与EMT核心诱导因子ZEB1相互作用，通过增强其泛素化修饰并促进蛋白酶体降解途径降低ZEB1蛋白水平。在A549和H1299细胞系中，内源性FBXO11的缺失会导致ZEB1蛋白积累并诱发EMT表型，而过表达FBXO11则能降低ZEB1蛋白丰度并抑制细胞侵袭能力。值得注意的是，敲低ZEB1可有效抑制由FBXO11缺失引起的A549和H1299细胞迁移和侵袭增强现象。异种移植瘤实验进一步验证了这一结论。临床预后分析表明，FBXO11高表达与NSLC患者良好预后相关。综上所述，本研究揭示了FBXO11通过调控ZEB1蛋白稳定性来调节肺癌细胞EMT进程的作用机制。

原文链接：

FBXO11 Mediates Ubiquitination of ZEB1 and Modulates Epithelial-to-Mesenchymal Transition in Lung Cancer Cells