Reduced expression of Axin correlates with tumour progression of oesophageal squamous cell carcinoma

The Wnt signalling pathway regulates cellular proliferation, differentiation, morphology, and motility in vertebrates and invertebrates (Zeng, 1997; Akiyama, 2000; Bienz and Clevers, 2000). Axin, a negative regulator of this pathway, promotes phosphorylation of serine/threonine in exon 3 of β-catenin by forming a complex with adenomatous polyposis coli (APC) and glycogen synthase kinase-3β (GSK-3β) (Ikeda et al, 1998, 2000; Kishida et al, 1998). Phosphorylated β-catenin is quickly degraded via a ubiquitin–proteasome pathway in the cytoplasm (Nakamura, 1997). Upon Wnt signalling, because the activity of Axin complex is blocked through Dishevelled, phosphorylation of β-catenin is suppressed and β-catenin accumulates in the cytoplasm. Accumulated β-catenin protein is translocated to the nucleus as a coactivator for the T-cell factor (TCF)/lymphocyte enhancer-binding factor (LEF) family (Morin et al, 1997; He et al, 1998) and activates the transcription of Wnt target genes such as c-myc (He et al, 1998) or cyclin D1 (Tetsu and McCormick, 1999).