Enhancement of GLI1-transcriptional activity by β-catenin in human cancer cells

The Hedgehog (Hh) signaling pathway and the Wnt signaling pathway are known to play important roles in carcinogenesis and the progression of various human malignant tumors. Although a relationship between these two pathways has recently been reported, the mechanism by which beta-catenin, one of the key molecules of the Wnt signaling pathway, influences the Hh pathway has not yet been revealed in detail. To clarify the role of beta-catenin in relation to the Hh signaling pathway, we transfected GLI1 and beta-catenin expression constructs into human malignant cells, including stomach, colon, and lung cancers, and evaluated the luciferase activity of GLI-responsive reporter constructs. While exogenous GLI1 increased the luciferase activity, exogenous beta-catenin also enhanced the activity under overexpression of GLI1. However, co-transfection with T-cell factor (TCF)-4 or lymphocyte enhancer factor (LEF)-1 did not influence the activity, indicating that the enhancement of beta-catenin in relation to the Hh signaling pathway is not TCF/LEF-dependent. Our results suggest that beta-catenin might be involved in the Hh signaling pathway via enhancement of the transcriptional activity of GLI.