He Hongchao, Dai Jun, Xu Zhaoping, He Wei, Wang Xiaojing, Zhu Yu, Wang Haofei
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.
Oncol Lett. 2018 Mar;15(3):3694-3702. doi: 10.3892/ol.2018.7744. Epub 2018 Jan 8.
F-box and WD repeat domain containing 7 (Fbxw7) is an F-box protein that belongs to the SKP1-CUL1-F-box protein E3 ligase complex and is responsible for transferring the ubiquitin molecule to the substrate, which results in its recognition and subsequent degradation by proteasomes. Furthermore, it can identify a network of signaling proteins that function in cell growth, diversion and apoptosis. In the present study, Fbxw7 was downregulated in renal cell carcinoma (RCC) tissues compared with the adjacent non-tumor tissues and its expression was significantly associated with the tumor-node-metastasis stage, lymph node metastasis and distant metastasis in patients with RCC. Furthermore, multivariate Cox regression analyses indicated that Fbxw7 expression was an independent factor for the prediction of the overall survival of patients with RCC. A functional study demonstrated that downregulation of Fbxw7 facilitated tumor cell migration and invasion via the epithelial-mesenchymal transition (EMT). Therefore, the results of the current study indicted that Fbxw7 is an anti-oncogene that serves a notable function in RCC development by suppressing RCC metastasis and the EMT, indicating the potential therapeutic value of Fbxw7 in inhibiting metastasis in RCC.
含F-box和WD重复结构域7（Fbxw7）是一种F-box蛋白，属于SKP1-CUL1-F-box蛋白E3连接酶复合物，负责将泛素分子转移至底物，使其被蛋白酶体识别并随后降解。此外，它能够识别在细胞生长、分化和凋亡中发挥作用的信号蛋白网络。在本研究中，与相邻非肿瘤组织相比，肾细胞癌（RCC）组织中Fbxw7表达下调，且其表达与RCC患者的肿瘤-淋巴结-转移分期、淋巴结转移及远处转移显著相关。此外，多因素Cox回归分析表明，Fbxw7表达是预测RCC患者总生存的独立因素。一项功能研究表明，Fbxw7表达下调通过上皮-间质转化（EMT）促进肿瘤细胞迁移和侵袭。因此，本研究结果表明Fbxw7是一种抑癌基因，通过抑制RCC转移和EMT在RCC发生发展中发挥重要作用，提示Fbxw7在抑制RCC转移方面具有潜在治疗价值。
