In the cancer stem cell niche of digestive tumors, the Hedgehog pathway engages in critical crosstalk with the Wnt pathway via its effector transcription factor GLI, either by directly upregulating Wnt ligand expression to activate Wnt signaling in neighboring cells in a paracrine manner, or by synergistically co-regulating a common set of downstream target genes with β-catenin in the nucleus, with both pathways working in concert to maintain the self-renewal capacity of cancer stem cells [129]. The gene discussed is GLI1; the disease is cancer.