Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts.
Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Cancer Res. 2021 Feb 1;81(3):517-524. doi: 10.1158/0008-5472.CAN-20-2720. Epub 2021 Jan 21.
Deregulation of the mRNA translational process has been observed during tumorigenesis. However, recent findings have shown that deregulation of translation also contributes specifically to cancer cell spread. During metastasis, cancer cells undergo changes in cellular state, permitting the acquisition of features necessary for cell survival, dissemination, and outgrowth. In addition, metastatic cells respond to external cues, allowing for their persistence under significant cellular and microenvironmental stresses. Recent work has revealed the importance of mRNA translation to these dynamic changes, including regulation of cell states through epithelial-to-mesenchymal transition and tumor dormancy and as a response to external stresses such as hypoxia and immune surveillance. In this review, we focus on examples of altered translation underlying these phenotypic changes and responses to external cues and explore how they contribute to metastatic progression. We also highlight the therapeutic opportunities presented by aberrant mRNA translation, suggesting novel ways to target metastatic tumor cells.
在肿瘤发生过程中观察到 mRNA 翻译过程的失调。然而,最近的研究结果表明,翻译的失调也特异性地促进了癌细胞的扩散。在转移过程中,癌细胞发生细胞状态的改变,从而获得细胞存活、扩散和生长所必需的特征。此外,转移细胞对外界信号作出反应,使其能够在显著的细胞和微环境压力下持续存在。最近的研究揭示了 mRNA 翻译对这些动态变化的重要性,包括通过上皮-间充质转化和肿瘤休眠来调节细胞状态,以及对缺氧和免疫监视等外部应激的反应。在这篇综述中,我们重点关注这些表型变化和对外界信号反应的基础上改变的翻译的例子,并探讨它们如何促进转移进展。我们还强调了异常 mRNA 翻译带来的治疗机会,提出了靶向转移性肿瘤细胞的新方法。