Shi Xingjuan, Sun Xiaoou
Key Laboratory of Developmental Genes and Human Disease, Institute of Life Sciences, Southeast University, Nanjing, 210096, China.
School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.
Cancer Chemother Pharmacol. 2017 Nov;80(5):909-917. doi: 10.1007/s00280-017-3398-2. Epub 2017 Jul 24.
Microtubules, highly dynamic components of the cytoskeleton, participate in diverse cellular activities such as mitosis, cell migration, and intracellular trafficking. Dysregulation of microtubule dynamics contributes to the development of serious diseases, including cancer. The dynamic properties and functions of microtubule network are regulated by microtubule-associated proteins. Paclitaxel, an anti-microtubule agent of the taxane family, has shown a success in clinical treatment of many cancer patients. However, the variable response activity of patients and acquired resistance to paclitaxel limit the clinical use of the drug. Accumulating studies show that microtubule-associated proteins can regulate paclitaxel sensitivity in a wide range of cancer types. In this review, we will describe the roles of various microtubule-associated proteins in the regulation of paclitaxel in cancers. Particularly, we will focus on the modulation of centrosomal proteins in paclitaxel resistance. Improved understandings of how these proteins act might predict treatment responses and provide insights into more rational chemotherapeutic regimens in clinical practice.
微管是细胞骨架中高度动态的成分，参与多种细胞活动，如细胞有丝分裂、细胞迁移和细胞内物质运输。微管动力学失调会导致包括癌症在内的严重疾病的发生。微管网络的动态特性和功能受微管相关蛋白调控。紫杉醇是一种紫杉烷类抗微管药物，已在许多癌症患者的临床治疗中取得成功。然而，患者的可变反应活性以及对紫杉醇的获得性耐药限制了该药物的临床应用。越来越多的研究表明，微管相关蛋白可在多种癌症类型中调节紫杉醇敏感性。在本综述中，我们将描述各种微管相关蛋白在癌症中调节紫杉醇方面的作用。特别地，我们将聚焦于中心体蛋白在紫杉醇耐药中的调节作用。对这些蛋白作用方式的深入理解可能有助于预测治疗反应，并为临床实践中更合理的化疗方案提供思路。
