The role of hydrogen peroxide-inducible clone-5 in tumor progression

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.