FICZ-induced, AhR-mediated skin carcinogenesis from UV radiation

FICZ (6-formylindolo[3,2-b]carbazole) is a tryptophan photoproduct in the skin, derived upon UVB exposure. FICZ is a high-affinity AhR agonist in which binding will trigger the canonical AhR pathway thus upregulating the expression of AhR target genes such as CYP1A1 [179]. When FICZ binds to the cytosolic AhR complex, cSrc is activated and dissociates from the complex. cSrc poses as a critical signal transducer for EGFR with substantial synergistic effects believed to exist between these proteins [180]. When EGFR is activated by EGF, the RAS/RAF/MEK/ERK signaling pathway is initiated, stimulating the expression of cyclooxygenase-2 (COX-2) [181]. COX-2 is widely implicated to promote tumorigenesis as it is believed to promote angiogenesis, immune evasion, and anti-apoptotic activity [182]. (Created with BioRender.com)

Publication

Targeting aryl hydrocarbon receptor to prevent cancer in barrier organs (2024) Francoise Congues, et al. Biochem Pharmacol. 2024 May 24;223(NA). Figure: F2. Homo sapiens

Disease mentions