Abstract
The β-catenin signaling is essential for maintaining the cancer stem cell phenotype, because that ablation of the β-catenin gene results in the loss of cancer stem cells and complete tumor regression. However, the precise action mechanism and downstream effectors of β-catenin signaling remain to be elucidated. In this study, we attempted to find the β-catenin-regulated gene in squamous cell carcinoma (SCC) cells. To identify the β-catenin-regulated genes in SCC cells, we overexpressed β-catenin using recombinant adenovirus in SCC13 cells, then screened the putative downstream genes. We found that CREB (cAMP response element binding protein 1) is upregulated by β-catenin in human SCC13 cell line. When β-catenin was overexpressed, the expression levels for CREB was significantly increased. To investigate the potential effect of CREB on cancer cell behavior, we overexpressed CREB using recombinant adenovirus in SCC13 cells. As a result, overexpression of CREB led to the marked increase of clonogenic activity. These results suggest that CREB is a β-catenin--regulated transcription factor that promotes cancer characteristics in SCC cells, providing new insight into the molecular mechanism underlying the regulation of cancer stemness by β-catenin in SCC.
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