Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada.
Oxid Med Cell Longev. 2017;2017:6098107. doi: 10.1155/2017/6098107. Epub 2017 Nov 26.
Hypoxia is an aspect of the tumor microenvironment that is linked to radiation and chemotherapy resistance, metastasis, and poor prognosis. The ability of hypoxic tumor cells to achieve these cancer hallmarks is, in part, due to changes in their gene expression profiles. Cancer cells have a high demand for protein synthesis, and translational control is subsequently deregulated. Various mechanisms of translation initiation are active to improve the translation efficiency of select transcripts to drive cancer progression. This review will focus on a noncanonical cap-dependent translation initiation mechanism that utilizes the eIF4E homolog eIF4E2, a hypoxia-activated cap-binding protein that is implicated in hypoxic cancer cell migration, invasion, and tumor growth in mouse xenografts. A historical perspective about eIF4E2 and its various aliases will be provided followed by an evaluation of potential therapeutic strategies. The recent successes of disabling canonical translation and eIF4E with drugs should highlight the novel therapeutic potential of targeting the homologous eIF4E2 in the treatment of hypoxic solid tumors.
缺氧是肿瘤微环境的一个方面，与放射治疗和化学疗法耐药性、转移和预后不良有关。缺氧肿瘤细胞能够实现这些癌症特征的部分原因是其基因表达谱发生了变化。癌细胞对蛋白质合成的需求很高，随后翻译控制失调。各种翻译起始机制都处于活跃状态，以提高选择转录本的翻译效率，从而推动癌症进展。这篇综述将重点介绍一种非典型的帽依赖性翻译起始机制，该机制利用了 eIF4E 同源物 eIF4E2，即一种缺氧激活的帽结合蛋白，它与缺氧癌细胞的迁移、侵袭和在小鼠异种移植物中的肿瘤生长有关。将提供关于 eIF4E2 及其各种别名的历史观点，然后评估潜在的治疗策略。用药物阻断经典翻译和 eIF4E 的最近成功应该突出了靶向同源 eIF4E2 在治疗缺氧实体瘤方面的新的治疗潜力。
