Cross-talk between Wnt and Hh signaling pathways in the pathology of basal cell carcinoma

Basal cell carcinoma (BCC) is the most frequently occurring form of all cancers. The cost of care for BCC is one of the highest for all cancers in the Medicare population in the United States. Activation of Hedgehog (Hh) signaling pathway appears to be a key driver of BCC development. Studies involving mouse models have provided evidence that activation of the glioma-associated oncogene (GLI) family of transcription factors is a key step in the initiation of the tumorigenic program leading to BCC. Activation of the Wnt pathway is also observed in BCCs. In addition, the Wnt signaling pathway has been shown to be required in Hh pathway-driven development of BCC in a mouse model. Cross-talks between Wnt and Hh pathways have been observed at different levels, yet the mechanisms of these cross-talks are not fully understood. In this review, we examine the mechanism of cross-talk between Wnt and Hh signaling in BCC development and its potential relevance for treatment. Recent studies have identified insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1), a direct target of the Wnt/β-catenin signaling, as the factor that binds to GLI1 mRNA and upregulates its levels and activities. This mode of regulation of GLI1 appears important in BCC tumorigenesis and could be explored in the treatment of BCCs.