Kong Fanyun, You Hongjuan, Tang Renxian, Zheng Kuiyang
Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China.
Oncol Lett. 2017 Apr;13(4):2514-2520. doi: 10.3892/ol.2017.5757. Epub 2017 Feb 22.
Hepatocellular carcinoma (HCC) is a major malignant disease worldwide, and chronic hepatitis B virus (HBV) infection is one of the primary causes for this type of cancer. Hepatitis B virus X protein (HBx) is a non-structural protein encoded by the viral genome that has significant effects on the pathogenesis of HCC. With the development of high-throughput assays and technologies, the abnormal HBx-induced expression of certain cellular proteins with assorted biological functions has been investigated. These target proteins identified by various methods include specific proteins associated with the cellular cytoskeleton, which contribute to HBx-induced hepatocarcinogenesis. In addition, the cytoskeletal proteins deregulated by HBx are involved in cell morphogenesis, adhesion, migration and proliferation. This review aims to summarize the current understanding of the expression profiles of HBx-associated cytoskeletal proteins, as well as their complex functions and underlying mechanisms in hepatocarcinogenesis. Considering that the potential therapeutics for various types of tumors may function through the stabilization of cytoskeletal proteins in order to restrict cellular movement and limit intracellular processes, clarifying the mechanisms underlying protein-associated cytoskeleton dysregulation by HBx may provide novel possibilities and potent therapeutic targets for HBV-associated HCC.
肝细胞癌(HCC)是全球主要的恶性疾病,慢性乙型肝炎病毒(HBV)感染是这类癌症的主要病因之一。乙型肝炎病毒X蛋白(HBx)是由病毒基因组编码的一种非结构蛋白,对HCC的发病机制有重大影响。随着高通量检测和技术的发展,已对异常的HBx诱导的具有各种生物学功能的某些细胞蛋白的表达进行了研究。通过各种方法鉴定出的这些靶蛋白包括与细胞骨架相关的特定蛋白,它们参与了HBx诱导的肝癌发生。此外,被HBx失调的细胞骨架蛋白参与细胞形态发生、黏附、迁移和增殖。本综述旨在总结目前对HBx相关细胞骨架蛋白表达谱及其在肝癌发生中的复杂功能和潜在机制的理解。鉴于各类肿瘤的潜在治疗方法可能通过稳定细胞骨架蛋白来发挥作用,以限制细胞运动并限制细胞内过程,阐明HBx导致蛋白相关细胞骨架失调的机制可能为HBV相关HCC提供新的可能性和有效的治疗靶点。