Dosedělová Lenka, Nekulová Marta, Zahradníková Martina, Faktor Jakub, Vojtěšek Bořivoj, Hernychová Lenka
Klin Onkol. 2018 Winter;31(Suppl 2):32-40. doi: 10.14735/amko20182S32.
The proteins of the cellular cytoplasmic membrane represent a heterogeneous group of proteins with different structures, localizations, and functions. They participate in many cellular processes including cellular signaling and communication with the external environment and communication between cells. Mutations and post-translational modifications alter the chemical-physical properties of membrane proteins and thus significantly affect the process of carcinogenesis. Therefore, membrane proteins represent important targets for the diagnosis and treatment of cancer. Nowadays, treatment in the form of monoclonal antibodies or low molecular weight inhibitors targets mainly receptors of growth factors on the surface of tumor cells and various types of molecules including the targets of the so-called checkpoint inhibitors on the surface of the cells of the immune system. In order to better understand the properties and functions of membrane proteins, especially with the perspective of developing new targeted approaches in therapy, mainly proteomic and molecular biological approaches are currently being used.
The aim of this article is to describe the properties and functions of different groups of membrane proteins and to summarize their current relevance and potential for use in oncology. Attention is focused on those groups that regulate the proliferation of tumor cells, affect the immune response, cause drug resistance and metastasis, and are already used or accepted as potential targets of biological therapy. Glycosylation and phosphorylation are described in detail as the most studied post-translational modification of membrane proteins, and mass spectrometry is presented as an effective tool for the identification and quantification of membrane proteins. Key words: membrane proteins - glycosylation - phosphorylation - proteomic analysis - targeted therapy This work was supported by the project MEYS - NPS I - LO1413. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Accepted: 3. 8. 2018.
细胞质膜蛋白是一组结构、定位和功能各异的异质性蛋白。它们参与许多细胞过程，包括细胞信号传导、与外部环境的通讯以及细胞间通讯。突变和翻译后修饰会改变膜蛋白的化学物理性质，从而显著影响致癌过程。因此，膜蛋白是癌症诊断和治疗的重要靶点。如今，以单克隆抗体或低分子量抑制剂形式的治疗主要针对肿瘤细胞表面的生长因子受体以及包括免疫系统细胞表面所谓检查点抑制剂靶点在内的各种类型分子。为了更好地了解膜蛋白的性质和功能，尤其是从开发新的靶向治疗方法的角度来看，目前主要使用蛋白质组学和分子生物学方法。
本文旨在描述不同组膜蛋白的性质和功能，并总结它们目前在肿瘤学中的相关性和应用潜力。重点关注那些调节肿瘤细胞增殖、影响免疫反应、导致耐药性和转移且已被用作或被视为生物治疗潜在靶点的蛋白组。详细描述了糖基化和磷酸化这两种研究最多的膜蛋白翻译后修饰，并介绍了质谱作为鉴定和定量膜蛋白的有效工具。关键词：膜蛋白 - 糖基化 - 磷酸化 - 蛋白质组学分析 - 靶向治疗 本研究得到了MEYS - NPS I - LO1413项目的支持。作者声明他们在研究中使用的药物、产品或服务方面不存在潜在利益冲突。编辑委员会声明该手稿符合ICMJE对生物医学论文的建议。接受日期：2018年8月3日。
