FIGURE 4.

The canonical Hedgehog signaling pathway involved in cancer and associated therapeutic targets. The secretion of HHN regulated by Dispatched homolog can bind to PTCH receptor and hence releases SMO. Then, accumulated SMO, sequestrated kinesin family member 7 (KIF7), suppressor of fused homolog (SUFU) proteins, and Gli transcription factors form a multiprotein complex in cilia, which prevents Gli from inhibitory phosphorylation by PKA. Stable Gli is further released from SUFU complex and mediates the transcription of Hedgehog signaling pathway. CAF‐derived hypoxia stimulates the expression of TGF‐β2, which increases the level of Gli2 and activates Hedgehog signaling. Meanwhile, SMO antagonists, HH inhibitors, and small molecular inhibitors were proven to inhibit hedgehog pathway activation.