Wnt-/-β-catenin pathway signaling in human hepatocellular carcinoma

Abstract

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: Beta catenin; Carcinoma; Hepatocellular; Receptors; Wnt proteins; Wnt signaling pathway.

Figure 1

Wnt-/-β-catenin signaling pathway. A: APC protein, axin, and GSK-3 that forms the complex destruction of the β-catenin protein in the proteasome; B: Wnt binds to Frizzled and LRP receptors, dissolving the destruction-complex, which results in an increase of β-catenin in the cytoplasm and nucleus. β-catenin forms a binding complex with the transcription factor LEF-/-TCF proteins to promote the activation of target genes. LRP: Lipoprotein receptor; Dvl: Dishevelled; APC: Adenomatous polyposis coli; GSK3: Glycogen synthase kinase 3; LET/TCF: Lymphoid enhancer factor/T-cell factor.