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 β-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 β-catenin in relation to the Hh signaling pathway, we transfected GLI1 and β-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 β-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 β-catenin in relation to the Hh signaling pathway is not TCF/LEF-dependent. Our results suggest that β-catenin might be involved in the Hh signaling pathway via enhancement of the transcriptional activity of GLI.

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