Alpha-actinin 4 and tumorigenesis of breast cancer.
Alpha-actinin 4 and tumorigenesis of breast cancer.
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DOI：
10.1016/b978-0-12-416673-8.00005-8
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发表时间：
2013
影响因子：
--
通讯作者：
Kao, Hung-Ying
中科院分区：
文献类型：
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作者：
Hsu, Kuo-Sheng;Kao, Hung-Ying
α-辅肌动蛋白（ACTNs）最初被鉴定为细胞骨架蛋白，其交联丝状肌动蛋白以建立保护细胞免受机械应力并控制细胞运动的细胞骨架架构。值得注意的是，与其他ACTN不同，α-辅肌动蛋白4（ACTN 4）在信号转导、核转位和基因表达调控中显示出独特的特征。最初的报道表明，ACTN 4是乳腺癌细胞运动装置的一部分，在细胞核中高度表达。这些结果表明，ACTN 4在乳腺癌肿瘤发生中起作用。虽然在乳腺癌和其他癌症中的一些观察结果支持这一假设，但几乎没有直接证据将肿瘤发生表型与ACTN 4介导的病理机制联系起来。最近，一些研究表明，除了协调细胞骨架的作用，ACTN 4与信号介质，染色质重塑因子和转录因子，包括核受体相互作用。因此，ACTN 4作为乳腺癌肿瘤发生的多功能启动子发挥作用，似乎是未来治疗开发的理想药物靶点。
Alpha-actinins (ACTNs) were originally identified as cytoskeletal proteins which cross-link filamentous actin to establish cytoskeletal architect that protects cells from mechanical stress and controls cell movement. Notably, unlike other ACTNs, alpha-actinin 4 (ACTN4) displays unique characteristics in signaling transduction, nuclear translocation, and gene expression regulation. Initial reports indicated that ACTN4 is part of the breast cancer cell motile apparatus and is highly expressed in the nucleus. These results imply that ACTN4 plays a role in breast cancer tumorigenesis. While several observations in breast cancer and other cancers support this hypothesis, little direct evidence links the tumorigenic phenotype with ACTN4-mediated pathological mechanisms. Recently, several studies have demonstrated that in addition to its role in coordinating cytoskeleton, ACTN4 interacts with signaling mediators, chromatin remodeling factors, and transcription factors including nuclear receptors. Thus, ACTN4 functions as a versatile promoter for breast cancer tumorigenesis and appears to be an ideal drug target for future therapeutic development.