Zhang Qiang, Zhang Yang, Hu Xuejiao, Qin Yuan, Zhong Weilong, Meng Jing, Xiao Ting, Zhang Chunhong, Li Meng, Chen Shuang, Liu Huijuan, Liu Yanrong, Sun Tao, Yang Cheng
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
Lab Invest. 2017 Aug;97(8):903-912. doi: 10.1038/labinvest.2017.51. Epub 2017 May 22.
Hepatocellular carcinoma (HCC) ranks as one of the most common and lethal malignancies worldwide. A better understanding of the mechanism responsible for HCC metastasis will be helpful for the treatment of HCC patients. Thymidine phosphorylase (TP), a key enzyme that catalyzes the conversion of thymidine to thymine and deoxyribose-1-phosphate, was demonstrated to promote the invasion and metastasis of HCC in our study. Clinical retrospective analysis revealed that metastatic HCC tumor tissues have higher TP expression, and TP expression was significantly correlated with matrix metalloproteinase (MMP) 2 and 9 expression. Survival analysis revealed that TP expression was negatively correlated with the prognosis of HCC patients. Moreover, in vitro cell experiments confirmed that TP could promote the migration and invasion of HCC cells. In addition, MMP2 and MMP9 were activated by TP overexpression. Overall, this study suggests that TP promotes metastasis and may serve as a marker of poor prognosis in HCC. Thus, TP is a potential target for the treatment of HCC.
肝细胞癌(HCC)是全球最常见且致命的恶性肿瘤之一。更好地了解HCC转移的机制将有助于治疗HCC患者。胸苷磷酸化酶(TP)是一种催化胸苷转化为胸腺嘧啶和脱氧核糖-1-磷酸的关键酶,在我们的研究中被证明可促进HCC的侵袭和转移。临床回顾性分析显示,转移性HCC肿瘤组织中TP表达较高,且TP表达与基质金属蛋白酶(MMP)2和9的表达显著相关。生存分析显示,TP表达与HCC患者的预后呈负相关。此外,体外细胞实验证实TP可促进HCC细胞的迁移和侵袭。另外,TP过表达可激活MMP2和MMP9。总体而言,本研究表明TP促进转移,可能是HCC预后不良的标志物。因此,TP是HCC治疗的潜在靶点。