Wu Wen-Sheng
Department of Laboratory Medicine and Biotechnology, College of Medicine, Tzu Chi University, Hualien, Taiwan.
Tzu Chi Med J. 2019 Aug 2;32(1):1-4. doi: 10.4103/tcmj.tcmj_120_19. eCollection 2020 Jan-Mar.
The poor prognosis of cancers such as hepatocellular carcinoma is due to high recurrence rate mainly caused by metastasis. Target therapy aiming at critical signal molecules within these pathways is one of the promising strategies for the prevention of metastasis. Hydrogen peroxide-inducible clone-5 (Hic-5), which belongs to the paxillin superfamily, is emerging as a potential target along the metastatic signaling pathway. Hic-5 and paxillin share similar structural features; however, there are a lot of different biochemical properties between them, including tissue-specific distribution, regulation of gene expression, critical signal cascade, and the impacts on cellular phenotypes. This review focus on the recent studies of Hic-5 related to its impacts on signal transduction and transcription responsible for tumor progression. Hic-5 may regulate mitogen-activated protein kinase cascade for cell migration and invasion in various systems. Hic-5 can mediate transforming growth factor-β1-induced epithelial-mesenchymal transition (EMT) via RhoA- and Src-dependent signaling. Moreover, Hic-5 plays a central role in a positive feedback Hic-5-NADPH oxidase-ROS-JNK signal cascade. This sustained signaling is required for regulating EMT-related genes including E-cadherin, Snail, MMP9, and Zeb-1. In addition, Hic-5 can be a transcription coregulatory factor for a lot of nuclear receptors. Owing to the critical role of Hic-5 in signal transduction and transcription responsible for tumor progression, it can be a potential therapeutic target for the prevention of tumor metastasis.
肝细胞癌等癌症预后较差，主要是由于转移导致的高复发率。针对这些信号通路中关键信号分子的靶向治疗是预防转移的一种有前景的策略。属于桩蛋白超家族的过氧化氢诱导克隆-5（Hic-5）正成为转移信号通路中的一个潜在靶点。Hic-5和桩蛋白具有相似的结构特征；然而，它们之间存在许多不同的生化特性，包括组织特异性分布、基因表达调控、关键信号级联以及对细胞表型的影响。本综述聚焦于Hic-5近期与其对肿瘤进展所负责的信号转导和转录影响相关的研究。Hic-5可能在各种系统中调节丝裂原活化蛋白激酶级联以促进细胞迁移和侵袭。Hic-5可通过RhoA和Src依赖的信号传导介导转化生长因子-β1诱导的上皮-间质转化（EMT）。此外，Hic-5在Hic-5-烟酰胺腺嘌呤二核苷酸磷酸氧化酶-活性氧-JNK信号正反馈级联中起核心作用。这种持续的信号传导对于调节包括E-钙黏蛋白、蜗牛蛋白、基质金属蛋白酶9和锌指蛋白E盒结合因子1等EMT相关基因是必需的。此外，Hic-5可以成为许多核受体的转录共调节因子。由于Hic-5在肿瘤进展所负责的信号转导和转录中起关键作用，它可能是预防肿瘤转移的一个潜在治疗靶点。
