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微管相关蛋白17与活性氧的双刃剑作用

MAP17 and the double-edged sword of ROS.

作者信息

Carnero Amancio

机构信息

Instituto de Biomedicina de Sevilla (IBIS), HUVR/CSIC/Universidad de Sevilla, Consejo Superior de Investigaciones Cientificas, Campus Hospital Universitario Virgen del Rocío, Sevilla, Spain.

出版信息

Biochim Biophys Acta. 2012 Aug;1826(1):44-52. doi: 10.1016/j.bbcan.2012.03.004. Epub 2012 Mar 23.

Abstract

Reactive oxygen species, ROS, are beneficially involved in many signaling pathways that control development and maintain cellular homeostasis. In physiological conditions, a tightly regulated redox balance protects cells from injurious ROS activity, but if the balance is altered, it promotes various pathological conditions including cancer. Understanding the duality of ROS as cytotoxic molecules and key mediators in signaling cascades may provide novel opportunities for improved cancer therapy. MAP17 is a small 17-kDa non-glycosylated membrane protein that is overexpressed in many tumors of different origins, including carcinomas. Immunohistochemical analysis of MAP17 during cancer progression demonstrates that overexpression of the protein strongly correlates with the progression of most types of tumor. Tumor cells that overexpress MAP17 show an increased tumoral phenotype associated with an increase in ROS. However, in non-tumor cells MAP17 increases ROS, resulting in senescence or apoptosis. Therefore, in tumor cells, MAP17 could be a marker for increased oxidative stress and could define new therapeutic approaches. Here, we review the role of MAP17 as a putative oncogene, as well as its role in cancer and anticancer therapies.

摘要

活性氧(ROS)有益地参与了许多控制发育和维持细胞稳态的信号通路。在生理条件下,严格调控的氧化还原平衡可保护细胞免受ROS有害活性的影响,但如果平衡被改变,则会促进包括癌症在内的各种病理状况。了解ROS作为细胞毒性分子和信号级联反应中的关键介质的双重性,可能为改进癌症治疗提供新的机会。MAP17是一种17 kDa的小分子非糖基化膜蛋白,在包括癌在内的许多不同起源的肿瘤中均有过表达。对癌症进展过程中MAP17的免疫组织化学分析表明,该蛋白的过表达与大多数类型肿瘤的进展密切相关。过表达MAP17的肿瘤细胞表现出与ROS增加相关的肿瘤表型增加。然而,在非肿瘤细胞中,MAP17会增加ROS,导致衰老或凋亡。因此,在肿瘤细胞中,MAP17可能是氧化应激增加的标志物,并可能定义新的治疗方法。在此,我们综述了MAP17作为一种假定癌基因的作用,以及它在癌症和抗癌治疗中的作用。

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