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Wnt/Frizzled signaling in hepatocellular carcinoma
Han Chu Lee1,Miran Kim1,Jack R Wands1
1
The Liver Research Center, Department of Medicine, Rhode Island Hospital, Brown Medical School, Providence, RI 02903, USA
DOI: 10.2741/1933 Volume 11 Issue 2, pp.1901-1915
Published: 01 May 2006
(This article belongs to the Special Issue WntFZD signalling in cancer and disease)
Abstract

The Wnt/Frizzled (FZD) signaling cascade is important for cell fate determination during embryonic development as well as maintaining tissue homeostasis in the adult. In addition to these physiologic roles, studies have shown that deregulation of Wnt/FZD signaling occurs during carcinogenesis. As an example, over 90% of the colorectal cancers have mutations in adenomatous polyposis coli (APC) or beta-catenin genes. In addition, hepatocellular carcinoma (HCC) is another tumor with frequent aberrant activation of beta-catenin signaling. Nuclear and/or cellular beta-catenin accumulation, a hallmark of the activated canonical Wnt/FZD signaling, has been observed in 33-67% of tumors. However, mutations of APC and/or beta-catenin genes are found only in about 20-30% of HCCs, suggesting that the predominant mechanism(s) activating Wnt/FZD signaling pathway may be different from that found in colorectal cancers. There is accumulating evidence to suggest that regulatory mechanisms other than mutations involving beta-catenin or proteins in its destruction complex, many of which involve upstream components of the Wnt/FZD cascade, are important in HCC. Furthermore, information on the target genes of Wnt/FZD signaling and their roles in hepatocarcinogenesis is limited despite the recent discovery of several candidate genes. This review focuses on the alterations of Wnt/FZD signaling pathways and their relationship to the pathogenesis of HCC. A better understanding of the precise mechanisms of altered Wnt/FZD signaling may provide new molecular targets for therapy of HCC.

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Han Chu Lee, Miran Kim, Jack R Wands. Wnt/Frizzled signaling in hepatocellular carcinoma. Frontiers in Bioscience-Landmark. 2006. 11(2); 1901-1915.