Zang Yuanwei, Zhang Xiang, Yan Lei, Gu Gangli, Li Dawei, Zhang Yongzhen, Fang Liang, Fu Shanshan, Ren Juchao, Xu Zhonghua
Department of Urology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan 250012, China.
Department of Gastroenterology, Shandong Provincial Qianfoshan Hospital, 16766 Jingshi Road, Jinan 250014, China.
J Cancer. 2017 Sep 2;8(15):3049-3061. doi: 10.7150/jca.19594. eCollection 2017.
Eukaryotic translation initiation factors (eIFs) constitute a new class of therapeutic cancer targets. EIF3b is the major scaffold protein of eIF3 (the largest core of eIFs). We sought to define the role played by and the mechanism of action of eIF3b in patients with clear cell renal cell carcinoma (ccRCC). We found that high-level eIF3b expression in tumors was not only associated with an aggressive tumor phenotype, but was also independently prognostic for patients with ccRCC. Knockdown of eIF3b impaired the action of the Akt pathway, thus inhibiting cell proliferation by disrupting the cell cycle and triggering apoptosis. Furthermore, the epithelial-to-mesenchymal transition was impaired after eIF3b depletion, via suppression of cell migration and invasion. Additionally, eIF3b knockdown significantly inhibited the growth of subcutaneous xenografts in mice. Together, these data show that eIF3b is both a promising prognostic biomarker and a potential therapeutic target for patients with ccRCC.
真核生物翻译起始因子（eIFs）构成了一类新的癌症治疗靶点。EIF3b是eIF3（eIFs最大的核心）的主要支架蛋白。我们试图确定EIF3b在透明细胞肾细胞癌（ccRCC）患者中所起的作用及其作用机制。我们发现肿瘤中高水平的EIF3b表达不仅与侵袭性肿瘤表型相关，而且也是ccRCC患者的独立预后因素。敲低EIF3b会损害Akt通路的作用，从而通过破坏细胞周期和触发凋亡来抑制细胞增殖。此外，在敲低EIF3b后，上皮-间质转化受到损害，这是通过抑制细胞迁移和侵袭实现的。此外，敲低EIF3b显著抑制了小鼠皮下异种移植瘤的生长。总之，这些数据表明EIF3b既是一种有前景的预后生物标志物，也是ccRCC患者的潜在治疗靶点。
