Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 18, 2015; 7(26): 2631-2635
Published online Nov 18, 2015. doi: 10.4254/wjh.v7.i26.2631
Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma
Jaques Waisberg, Gabriela Tognini Saba
Jaques Waisberg, Department of Surgery, Hospital do Servidor Público Estadual de São Paulo (IAMSPE), São Paulo 09060-650, Brazil
Jaques Waisberg, Gabriela Tognini Saba, Department of Surgery, ABC Medical School, Santo André, São Paulo 09060-650, Brazil
Author contributions: Waisberg J and Saba GT contributed equally to this work.
Conflict-of-interest statement: The authors have no conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jaques Waisberg, MD, PhD, FACS, Professor, Head, Department of Surgery, ABC Medical School, Santo André, São Paulo 09060-650, Brazil. jaqueswaisberg@uol.com.br
Telephone: +55-11-982560018 Fax: +55-11-44368739
Received: May 28, 2015
Peer-review started: June 1, 2015
First decision: July 27, 2015
Revised: October 12, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: November 18, 2015

The molecular basis of the carcinogenesis of hepatocellular carcinoma (HCC) has not been adequately clarified, which negatively impacts the development of targeted therapy protocols for this overwhelming neoplasia. The aberrant activation of signaling in the HCC is primarily due to the deregulated expression of the components of the Wnt-/-β-catenin. This leads to the activation of β-catenin/T-cell factor-dependent target genes that control cell proliferation, cell cycle, apoptosis, and cell motility. The deregulation of the Wnt pathway is an early event in hepatocarcinogenesis. An aggressive phenotype was associated with HCC, since this pathway is implicated in the proliferation, migration, and invasiveness of cancer cells, regarding the cell’s own survival. The disruption of the signaling cascade Wnt-/-β-catenin has shown anticancer properties in HCC’s clinical evaluations of therapeutic molecules targeted for blocking the Wnt signaling pathway for the treatment of HCC, and it represents a promising perspective. The key to bringing this strategy in to clinical practice is to identify new molecules that would be effective only in tumor cells with aberrant signaling β-catenin.

Keywords: Carcinoma, Hepatocellular, Wnt signaling pathway, Beta catenin, Wnt proteins, Receptors

Core tip: The Wnt signaling pathway is decisive in the rule of mechanisms of proliferation and survival, as well as the differentiation of liver cells during hepatic embryogenesis and morphogenesis. The atypical initiation of signaling in the hepatocellular carcinoma (HCC) is primarily because of deregulated expressions of the components of the Wnt-/-β-catenin. The mechanisms that are considered more functional and that sustain aberrant activation of signaling pathways act via alterations in the β-catenin gene or the AXIN1/2-gene’s encoding axin, a protein necessary for the degradation of β-catenin. The development of targeted therapeutic molecules for the blockade of the Wnt-signaling pathway for the treatment of HCC depends on the identification of molecules that would be effective only in tumor cells that carry an aberrant signaling β-catenin.