Human T-Cell factor-4 isoform promotes tumorigenicity in a hypoxia-dependent manner

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The Wnt signaling pathway plays a major role in development and carcinogenesis. Its downstream gene expressions occur through T-cell factor (TCF) proteins. We previously identified and cloned 14 human TCF-4 isoforms, and focused on function of the unique motif SxxSS in the isoforms. In our three-year study, we have demonstrated that loss of the SxxSS motif in a TCF-4 isoform confers hypoxia resistance to liver cancer cells, possibly resulting in augmented tumorigenesis. One of the underlying mechanisms was increased expression levels of HIF-2alpha through down-regulated expression of VHL.