Zhao Xinyue, Han Zhihui, Liu Ruiying, Li Zehao, Mei Ling, Jin Yue
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun 130012, China.
National Engineering Laboratory of AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China.
Cancers (Basel). 2024 Sep 26;16(19):3269. doi: 10.3390/cancers16193269.
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.
上皮-间质转化（EMT）影响癌细胞的侵袭和迁移。在此，我们表明FBXO11识别并促进ZEB1的泛素介导降解。在临床数据库中，非小细胞肺癌（NSCLC）中FBXO11与ZEB1之间存在强关联。FBXO11与EMT的核心诱导因子ZEB1相互作用。FBXO11导致ZEB1的泛素化增加和蛋白酶体降解。内源性FBXO11的缺失导致A549和H1299细胞中ZEB1蛋白积累和EMT，而FBXO11的过表达降低ZEB1蛋白丰度和细胞侵袭性。重要的是，ZEB1的缺失抑制了由FBXO11缺失促进的A549和H1299细胞迁移和侵袭增加。异种移植肿瘤中也显示出相同的结果。FBXO11高表达与NSCLC的良好预后相关。总体而言，我们的研究表明FBXO11通过介导肺癌细胞中ZEB1的稳定性来调节EMT。
