Zhu Wei, Li Gui Xian, Chen Hong Lang, Liu Xing Yan
Department of Pathology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
Department of Pharmacology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.
Oncol Lett. 2017 Jul;14(1):3-9. doi: 10.3892/ol.2017.6161. Epub 2017 May 12.
Eukaryotic translation initiation factor 6 (eIF6) affects the maturation of 60S ribosomal subunits. Found in yeast and mammalian cells, eIF6 is primarily located in the cytoplasm of mammalian cells. Emerging evidence has demonstrated that the dysregulated expression of eIF6 is important in several types of human cancer, including head and neck carcinoma, colorectal cancer, non-small cell lung cancer and ovarian serous adenocarcinoma. However, the molecular mechanisms by which eIF6 functions during tumor formation and progression remain elusive. The present review focuses on recent progress in terms of the mechanisms and functions of eIF6 in human tumorigenesis or cancer cell lines, along with the signal transduction pathways in which this novel translation initiation factor may participate. Oncogenic Ras activates Notch-1 and promotes transcription of eIF6 via a recombining binding protein suppressor of Hairless-dependent mechanism. In addition, overexpression of eIF6 results in aberrant activation of the Wnt/β-catenin signaling pathway. Similarly, overexpressed eIF6 regulates its downstream modulator, cell division control protein 42, which in turn affects oncogenesis. Finally, the potential of eIF6 as a biomarker for diagnosis of cancer is also discussed in the present review.
真核生物翻译起始因子6(eIF6)影响60S核糖体亚基的成熟。eIF6存在于酵母和哺乳动物细胞中,主要位于哺乳动物细胞的细胞质中。新出现的证据表明,eIF6表达失调在几种类型的人类癌症中具有重要作用,包括头颈癌、结直肠癌、非小细胞肺癌和卵巢浆液性腺癌。然而,eIF6在肿瘤形成和进展过程中发挥作用的分子机制仍不清楚。本综述重点关注eIF6在人类肿瘤发生或癌细胞系中的机制和功能方面的最新进展,以及这种新型翻译起始因子可能参与的信号转导途径。致癌性Ras通过一种依赖无毛重组结合蛋白抑制因子的机制激活Notch-1并促进eIF6的转录。此外,eIF6的过表达导致Wnt/β-连环蛋白信号通路的异常激活。同样,过表达的eIF6调节其下游调节因子细胞分裂控制蛋白42,进而影响肿瘤发生。最后,本综述还讨论了eIF6作为癌症诊断生物标志物的潜力。