Review
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Clin Oncol. Aug 10, 2011; 2(8): 311-325
Published online Aug 10, 2011. doi: 10.5306/wjco.v2.i8.311
Dickkopfs and Wnt/β-catenin signalling in liver cancer
Sarwat Fatima, Nikki P Lee, John M Luk
Sarwat Fatima, Nikki P Lee, Department of Surgery, The University of Hong Kong, Hong Kong, China
John M Luk, Department of Pharmacology and Surgery, National University Health System, Singapore 117597, Singapore
John M Luk, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117456, Singapore
John M Luk, Institute of Molecular and Cell Biology, A*STAR Singapore, Singapore 138673, Singapore
Author contributions: Fatima S designed and wrote the manuscript; Lee NP and Luk JM edited, advised and supervised this work.
Correspondence to: John M Luk, Professor, Cancer Science Institute of Singapore, National University of Singapore, Singapore 117456, Singapore. jmluk@nus.edu.sg
Telephone: +65-65164516 Fax: +65-68737690
Received: June 13, 2011
Revised: July 7, 2011
Accepted: July 14, 2011
Published online: August 10, 2011
Abstract

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.

Keywords: Dickkopf; Hepatocellular carcinoma; Tumourigenesis; Wnt/β-catenin signalling