Microtubules and their role in cellular stress in cancer.
Microtubules and their role in cellular stress in cancer.
复制标题
微管及其在癌症细胞应激中的作用。
DOI：
10.3389/fonc.2014.00153
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发表时间：
2014
影响因子：
4.7
通讯作者：
McCarroll JA
中科院分区：
文献类型：
--
作者：
Parker AL;Kavallaris M;McCarroll JA
微管是高度动态的结构，其由α-和β-微管蛋白异源二聚体组成，并且参与细胞运动、细胞内运输和有丝分裂。在癌症的背景下，微管蛋白家族蛋白被认为是微管蛋白结合化疗剂的靶标，其抑制有丝分裂纺锤体的动力学以引起有丝分裂停滞和细胞死亡。重要的是，微管稳定性的变化和不同微管蛋白同种型的表达以及改变的翻译后修饰已被报道用于一系列癌症。这些变化与实体癌和血液癌的预后不良和化疗耐药性相关。然而，这些观察结果背后的机制仍然知之甚少。新出现的证据表明，微管蛋白和微管相关蛋白可能在一系列细胞应激反应中发挥作用，从而赋予癌细胞生存优势。本文将重点介绍微管蛋白网络在调节应激反应中的重要作用。了解微管在这种情况下的作用，可能会提供新的治疗癌症的治疗方法。
Microtubules are highly dynamic structures, which consist of α- and β-tubulin heterodimers, and are involved in cell movement, intracellular trafficking, and mitosis. In the context of cancer, the tubulin family of proteins is recognized as the target of the tubulin-binding chemotherapeutics, which suppress the dynamics of the mitotic spindle to cause mitotic arrest and cell death. Importantly, changes in microtubule stability and the expression of different tubulin isotypes as well as altered post-translational modifications have been reported for a range of cancers. These changes have been correlated with poor prognosis and chemotherapy resistance in solid and hematological cancers. However, the mechanisms underlying these observations have remained poorly understood. Emerging evidence suggests that tubulins and microtubule-associated proteins may play a role in a range of cellular stress responses, thus conferring survival advantage to cancer cells. This review will focus on the importance of the microtubule–protein network in regulating critical cellular processes in response to stress. Understanding the role of microtubules in this context may offer novel therapeutic approaches for the treatment of cancer.