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. 2021 Oct 26;7:314. doi: 10.1038/s41420-021-00679-7

Fig. 3. Inhibition of Hh signalling prevents tumourigenesis and CAC progression.

Fig. 3

Shh inhibitors, including cerulenin and itraconazole, play a potent suppressing role on carcinogenesis-associated inflammation by downregulating IL-6, IL-6-associated signal transducer and activator of transcription 3 (STAT3) signalling, and NF-κB-related TNF-α. Moreover, Shh inhibitors induce apoptosis by elevating cleaved caspase-3 and exert an anti-proliferating effect by elevating 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin E2 (PGE2)-degrading and tumour-suppressive enzyme. This subsequently inhibits cyclooxygenase-2 (COX-2). In addition, activation of Hh signalling by TNF-α/NF-κB-generated overexpression of the histone demethylase, JMJD2D, can be impaired by DSS or AOM/DSS and promotes tumourigenesis and CAC metastasis. Blue lines indicate evidence from two separate studies. Arrows, blunt ends, and dotted lines indicate activation, inhibition, and indirect regulatory effects, respectively. 15-PGDH 15-hydroxyprostaglandin dehydrogenase, PGE2 prostaglandin E2, COX-2 cyclooxygenase-2; IL-6 interleukin-6, STAT3 signal transducer and activator of transcription 3, JMJD2D jumonji domain-containing protein 2D, TNF-α/NF-κB Tumour necrosis factor-α/nuclear factor-kappaB.