Published online Nov 18, 2015. doi: 10.4254/wjh.v7.i26.2631
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.
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.