Figure 1

The Wnt/β-catenin signaling pathway. A) In the absence of Wnt ligands such as Wnt1, Wnt3a, and Wnt8 (“off” state), β-catenin is degraded by the APC/Axin/GSK-3ß complex. B) Binding of Wnt ligands to the Frizzled transmembrane receptors and their LRP co-receptors (“on” state) leads to the inactivation of GSK-3ß and accumulation of β-catenin in the cytoplasm. Then, the elevated cytosolic β-catenin can translocate to the nucleus, where it interacts with the Tcf/LEF transcription factors, leading to transcriptional activation of Wnt-responsive genes. Many Wnt-responsive genes have crucial roles in cell proliferation, migration, and invasion. Two fungal derivatives (PKF 115–854 and CGP049090), small-molecule antagonists of the Tcf/β-catenin complex, disrupt the critical protein-protein interaction between β-catenin and Tcf as indicated in this figure. Effects of PKF 115–854 and/or CGP049090 on endometriosis are summarized in Table 1. APC: adenomatous polyposis coli, GSK-3ß: glycogen synthase kinase 3β, LRP: lipoprotein receptor-related protein, TCF/LEF: T-cell factor/lymphocyte enhancer factor, CK1: casein kinase, DVL: disheveled.