fig1

Figure 1. Mechanism of Wnt/β-catenin signaling and potential molecular alterations that may affect β-catenin signaling. A: In the absence of Wnt binding at the cell membrane, β-catenin is kept in check by a large destruction complex comprised of Axin, DVL, CK1, GSK3, and APC; B: Wnt binding to Frizzled and LRP5/6 sequesters Axin and its associated molecules increases the abundance of unphosphorylated β-catenin to enhance classical Wnt/β-catenin signaling; C: as the most frequent causes of aberrant β-catenin signaling in HCC, CTNNB1 exon 3 mutations protect β-catenin from GSK3-mediated phosphorylation, leading to an increase in the amount of stable β-catenin that can enter the nucleus; D: in addition to mutations, other molecular alterations (indicated in red) can lead to aberrant Wnt/β-catenin activity to consequently promote a myriad of changes in tumor phenotype. Lipoprotein receptor related proteins 5 and 6 (LRP5/6), dishevelled protein (DVL), adenomatous polyposis coli (APC), casein kinase 1 (CK1), glycogen synthase kinase 3 (GSK3), T cell factor (TCF), glypican-3 (GPC-3), soluble frizzled related protein (SFRP), and E-cadherin (Cad)