University of Maryland School of Medicine, Baltimore, Maryland.
Veterans Administration Medical Center, Baltimore, Maryland.
Mol Cancer Ther. 2019 Sep;18(9):1475-1483. doi: 10.1158/1535-7163.MCT-19-0307.
Cancer cells revamp the regulatory processes that control translation to induce tumor-specific translational programs that can adapt to a hostile microenvironment as well as withstand anticancer therapeutics. Translational initiation has been established as a common downstream effector of numerous deregulated signaling pathways that together culminate in prooncogenic expression. Other mechanisms, including ribosomal stalling and stress granule assembly, also appear to be rewired in the malignant phenotype. Therefore, better understanding of the underlying perturbations driving oncogenic translation in the transformed state will provide innovative therapeutic opportunities. This review highlights deubiquitinating enzymes that are activated/dysregulated in hematologic malignancies, thereby altering the translational output and contributing to tumorigenesis.
癌细胞改变了控制翻译的调节过程，诱导肿瘤特异性翻译程序，使肿瘤能够适应恶劣的微环境并耐受抗癌治疗。翻译起始已被确定为许多失调信号通路的共同下游效应物，这些信号通路共同导致致癌表达。其他机制，包括核糖体停滞和应激颗粒组装，在恶性表型中似乎也被重新布线。因此，更好地了解驱动转化状态致癌翻译的潜在扰动将提供创新的治疗机会。这篇综述强调了在血液恶性肿瘤中被激活/失调的去泛素化酶，从而改变翻译产物并促进肿瘤发生。
