Epigenetic regulation of hepatic tumor-initiating cells
Epigenetic regulation of hepatic tumor-initiating cells
复制标题
肝肿瘤起始细胞的表观遗传调控
DOI：
10.2741/4349
复制
发表时间：
2015-06-01
影响因子：
3.1
通讯作者：
Wu, Jian
中科院分区：
文献类型：
--
作者：
Ding, Jia;Wu, Jian
肝细胞癌（HCC）是第三大致死性癌症，对常规化疗耐药。肿瘤起始细胞（T-IC）被认为是负责肿瘤发生的细胞，其表面标志物和信号通路与正常组织干细胞相似。识别T-IC和阐明异常的表观遗传调节和自我更新途径可能为肝癌的发生、转移和化疗耐药提供新的见解。组蛋白修饰、DNA甲基化和微环境变化被认为是促进T-ICs衍生和功能的关键因素。本文就正常肝干细胞和T-ICs的异同进行了比较，并对导致正常肝干细胞向T-ICs转化的内在因素和环境因素进行了阐述。我们认为病因学、微环境改变、表观遗传修饰和上皮-间质转化在启动转化中起着基础性作用。针对调节这些过程的关键信号分子的策略可能会在未来为HCC提供个性化治疗。
Hepatocellular carcinoma (HCC) is the third most lethal cancer and resistant to common chemotherapy. Tumor-initiating cells (T-ICs) that are thought to be responsible for tumorigenesis share surface markers and signaling pathways similar to normal tissue stem cells. Identification of T-ICs and elucidation of aberrant epigenetic modulation and self-renewal pathways may provide new insights into hepatic carcinogenesis, metastasis and chemotherapeutic resistance. Histone modification, DNA methylation and microenvironmental changes are considered as key elements to promote the derivation and function of T-ICs. In this review, we intend to compare the similarity and difference between normal liver stem cells and T-ICs, and to define the intrinsic and environmental factors that lead to the transformation from normal liver stem cells to hepatic T-ICs. We believe that etiology, microenvironmental alteration, epigenetic modification and epithelial-mesenchymal transition play a fundamental role in initiating the transformation. Strategies targeting signaling molecules critical in modulating these processes may offer a personalized therapy for HCC in the future.