Although the number of new cases of basal cell carcinoma (BCC) has increased rapidly in the last few decades, the molecular basis of its pathogenesis is not completely understood. Activation of the Hedgehog (Hh) signaling pathway has been shown to be a key factor driving the development of BCC. The Wnt/β-catenin signaling pathway was also shown to be activated in BCCs and to perhaps modulate the activity of the Hh pathway. We have previously identified a mechanism by which Wnt signaling regulates the transcriptional outcome of the Hh signaling pathway. We demonstrated that coding region determinant-binding protein (CRD-BP), a direct target of the Wnt/β-catenin signaling, binds to GLI1 mRNA, stabilizes it, and consequently upregulates its levels (mRNA and protein) and activities. We hypothesized that Wnt-induced and CRD-BP-dependent regulation of GLI1 expression and activities is important for the development of BCC. In this study, we show that CRD-BP is overexpressed in BCC and that its expression positively correlates with the activation of both Wnt and Hh signaling pathways. We also describe the generation and characterization of a human BCC cell line. This cell line was utilized to demonstrate the importance of CRD-BP-dependent regulation of GLI1 expression and activities in the development of BCC.
Bibliographical noteFunding Information:
We thank the Department of Dermatology at UW Madison for providing logistics during the collection of the BCC samples, I Siddiqui for helping with the generation of tumors in nude mice, and K Spiegelman for editing the manuscript. This work was supported by a Dermatology Foundation Career Development Award (to FKN) and NIH grants CA153102 (to FKN), CA121851, and AR063361 (to VSS).