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从癌细胞质膜评估脂质对信号级联反应调控的理解和多学科方法的进展。

Advances in understanding and in multi-disciplinary methodology used to assess lipid regulation of signalling cascades from the cancer cell plasma membrane.

机构信息

School of Food Science and Nutrition, University of Leeds, Leeds LS29JT, UK; Leeds Institute of Cardiovascular and Metabolic Medicine and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK; Molecular and Nanoscale Physics Group, School of Physics and Astronomy, University of Leeds, Leeds LS2 9JT, UK.

Leeds Institute of Cardiovascular and Metabolic Medicine and Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, UK.

出版信息

Prog Lipid Res. 2021 Jan;81:101080. doi: 10.1016/j.plipres.2020.101080. Epub 2020 Dec 24.

DOI:10.1016/j.plipres.2020.101080
PMID:33359620
Abstract

The lipid bilayer is a functional component of cells, forming a stable platform for the initiation of key biological processes, including cell signalling. There are distinct changes in the lipid composition of cell membranes during oncogenic transformation resulting in aberrant activation and inactivation of signalling transduction pathways. Studying the role of the cell membrane in cell signalling is challenging, since techniques are often limited to by timescale, resolution, sensitivity, and averaging. To overcome these limitations, combining 'computational', 'wet-lab' and 'semi-dry' approaches offers the best opportunity to resolving complex biological processes involved in membrane organisation. In this review, we highlight analytical tools that have been applied for the study of cell signalling initiation from the cancer cell membranes through computational microscopy, biological assays, and membrane biophysics. The cancer therapeutic potential of extracellular membrane-modulating agents, such as cholesterol-reducing agents is also discussed, as is the need for future collaborative inter-disciplinary research for studying the role of the cell membrane and its components in cancer therapy.

摘要

脂质双层是细胞的功能组成部分,为包括细胞信号转导在内的关键生物过程的启动提供了稳定的平台。致癌转化过程中细胞膜的脂质组成会发生明显变化,导致信号转导途径的异常激活和失活。研究细胞膜在细胞信号转导中的作用具有挑战性,因为技术通常受到时间尺度、分辨率、灵敏度和平均水平的限制。为了克服这些限制,结合“计算”、“湿实验室”和“半干”方法为解决涉及膜组织的复杂生物过程提供了最佳机会。在这篇综述中,我们强调了通过计算显微镜、生物测定和膜生物物理学应用于研究从癌细胞膜起始的细胞信号转导的分析工具。还讨论了细胞外膜调节因子(如胆固醇还原剂)在癌症治疗中的潜在治疗作用,以及未来跨学科合作研究在研究细胞膜及其成分在癌症治疗中的作用方面的必要性。

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