Fatima Sarwat, Lee Nikki P, Luk John M
Sarwat Fatima, Nikki P Lee, Department of Surgery, The University of Hong Kong, Hong Kong, China.
World J Clin Oncol. 2011 Aug 10;2(8):311-25. doi: 10.5306/wjco.v2.i8.311.
Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/β-catenin pathway for potential therapy of HCC.
肝癌分别是男性和女性中第五和第七大常见癌症病因。Wnt/β-连环蛋白信号通路已成为正常肝脏发育以及肝细胞癌（HCC）致癌驱动因素中的关键参与者。基于目前的认识，本文总结了该通路异常激活的可能机制，特别关注肝细胞癌。此外，我们将讨论 dickkopf 蛋白（DKKs）在调节 Wnt/β-连环蛋白信号通路中的作用，目前对此了解甚少且研究不足。DKKs 是一类分泌蛋白家族，至少包括四个成员，即 DKK1 - DKK4，它们作为 Wnt/β-连环蛋白信号通路的抑制剂。然而，并非所有成员都拮抗 Wnt/β-连环蛋白信号通路。它们在肝癌发生中的功能意义仍有待进一步明确，这些研究应为 DKKs 在肝癌发生中 Wnt/β-连环蛋白信号通路的调节作用提供新的见解。由于其重要的致癌作用，越来越多的治疗分子靶向β-连环蛋白和 Wnt/β-连环蛋白通路用于肝细胞癌的潜在治疗。
