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机械信号对蛋白质合成与稳定性的调控及其在癌症中的意义

Regulation of protein synthesis and stability by mechanical cues and its implications in cancer.

作者信息

Göransson Sara, Strömblad Staffan

机构信息

Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Sweden.

Department of Biosciences and Nutrition, Karolinska Institutet, SE-141 83 Huddinge, Sweden.

出版信息

Curr Opin Cell Biol. 2024 Feb;86:102304. doi: 10.1016/j.ceb.2023.102304. Epub 2023 Dec 18.

Abstract

Elevated tissue stiffness is a common feature of many solid tumors and the downstream mechanical signaling affects many cellular processes and contributes to cancer progression. Significant progress has been made in understanding how the mechanical properties of the matrix affect cancer cell behavior as well as transcription. However, how the same mechanical cues impact protein synthesis and stability and how this may contribute to disease is less well understood. Here, we present emerging evidence that cancer progression is frequently supported by gene regulation acting beyond the mRNA level and highlight some of the known crosstalk between this type of regulation and mechanotransduction in cancer as well as in other contexts. We suggest that future systematic approaches to define mechanosensitive translatomes and proteomes and how these are controlled may provide novel targets for cancer therapy.

摘要

组织硬度升高是许多实体瘤的共同特征,下游机械信号影响许多细胞过程并促进癌症进展。在理解基质的机械特性如何影响癌细胞行为以及转录方面已经取得了重大进展。然而,相同的机械信号如何影响蛋白质合成和稳定性以及这如何导致疾病,人们了解得较少。在这里,我们展示了新出现的证据,即癌症进展通常由mRNA水平之外的基因调控所支持,并强调了这种调控类型与癌症以及其他情况下的机械转导之间的一些已知相互作用。我们建议,未来用于定义机械敏感翻译组和蛋白质组以及它们如何被控制的系统方法可能为癌症治疗提供新的靶点。

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