Cai Sicheng, Deng Yue, Peng Huiming, Shen Jian
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Human Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Oncol. 2021 Sep 3;11:723341. doi: 10.3389/fonc.2021.723341. eCollection 2021.
Hepatocellular carcinoma (HCC) is characterized by high prevalence, morbidity, and mortality. Liver cancer is the sixth most common cancer worldwide; and its subtype, HCC, accounts for nearly 80% of cases. HCC progresses rapidly, and to date, there is no efficacious treatment for advanced HCC. Tetraspanins belong to a protein family characterized by four transmembrane domains. Thirty-three known tetraspanins are widely expressed on the surface of most nucleated cells and play important roles in different biological processes. In our review, we summarize the functions of tetraspanins and their underlying mechanism in the life cycle of HCC, from its initiation, progression, and finally to treatment. CD9, TSPAN15, and TSPAN31 can promote HCC cell proliferation or suppress apoptosis. CD63, CD151, and TSPAN8 can also facilitate HCC metastasis, while CD82 serves as a suppressor of metastasis. TSPAN1, TSPAN8, and CD151 act as prognosis indicators and are inversely correlated to the overall survival rate of HCC patients. In addition, we discuss the potential of role of the tetraspanin family proteins as novel therapeutic targets and as an approach to overcome drug resistance, and also provide suggestions for further research.
肝细胞癌（HCC）具有高发病率、高致残率和高死亡率的特点。肝癌是全球第六大常见癌症，其亚型HCC占病例总数的近80%。HCC进展迅速，迄今为止，对于晚期HCC尚无有效的治疗方法。四跨膜蛋白属于一个以四个跨膜结构域为特征的蛋白质家族。已知的33种四跨膜蛋白广泛表达于大多数有核细胞表面，并在不同的生物学过程中发挥重要作用。在我们的综述中，我们总结了四跨膜蛋白在HCC生命周期中的功能及其潜在机制，从其起始、进展到最终治疗。CD9、TSPAN15和TSPAN31可促进HCC细胞增殖或抑制细胞凋亡。CD63、CD151和TSPAN8也可促进HCC转移，而CD82则作为转移抑制因子。TSPAN1、TSPAN8和CD151作为预后指标，与HCC患者的总生存率呈负相关。此外，我们讨论了四跨膜蛋白家族蛋白作为新型治疗靶点以及克服耐药性方法的潜在作用，并为进一步研究提供了建议。
