Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective.
Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective.
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DOI：
10.3727/105221616x693639
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发表时间：
2017-02-10
期刊：
影响因子：
--
通讯作者：
Monga SP
中科院分区：
文献类型：
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作者：
Bell D;Ranganathan S;Tao J;Monga SP
肝母细胞瘤是最常见的儿童肝脏恶性肿瘤，通常发生在儿童出生后 3 年内。虽然化疗和更新的手术技术的进步提高了局部疾病患者的生存率，但不幸的是，对于 25% 的转移患者来说，总体生存率仍然很差。这些肿瘤被认为是由肝祖细胞或成肝细胞产生的，因此被称为肝母细胞瘤，可以根据细胞分化水平通过组织学亚型进行分类。对人类肿瘤样本的基因组和组织学分析显示，高达 90% 的肝母细胞瘤病例中，β-连环蛋白（Wnt 信号通路的下游效应子）编码基因中存在外显子 3 缺失或错义突变。本文将回顾与肝母细胞瘤各种亚型相关的分子途径的关键畸变，重点关注 Wnt 信号传导。它还将讨论 β-连环蛋白和 Yes 相关蛋白等途径成分在癌症发展中的合作。了解肿瘤发生中分子信号传导的复杂网络无疑将有助于发现新的治疗方法来帮助对抗肝母细胞瘤。
Hepatoblastoma is the most common pediatric liver malignancy, typically striking children within the first 3 years of their young lives. While advances in chemotherapy and newer surgical techniques have improved survival in patients with localized disease, unfortunately, for the 25% of patients with metastasis, the overall survival remains poor. These tumors, which are thought to arise from hepatic progenitors or hepatoblasts, hence the name hepatoblastoma, can be categorized by histological subtyping based on their level of cell differentiation. Genomic and histological analysis of human tumor samples has shown exon-3 deletions or missense mutations in gene coding for β-catenin, a downstream effector of the Wnt signaling pathway, in up to 90% of hepatoblastoma cases. The current article will review key aberrations in molecular pathways that are implicated in various subtypes of hepatoblastoma with an emphasis on Wnt signaling. It will also discuss cooperation among components of pathways such as β-catenin and Yes-associated protein in cancer development. Understanding the complex network of molecular signaling in oncogenesis will undoubtedly aid in the discovery of new therapeutics to help combat hepatoblastoma.