Involvement of Cell Proliferation Induced by Dual Intracellular Signaling of HB-EGF in the Development of Colitis-Associated Cancer during Ulcerative Colitis
Figure 2
Dual HB-EGF signaling induced by IL-8. Quoted from [46] and modified. IL-8 binds to the GPCR, thereby inducing ADAM10-mediated cleavage of proHB-EGF, resulting in ectodomain shedding of its N-terminus and the generation of an intracellular C-terminal fragment (HB-EGF-CTF). The shed soluble HB-EGF binds to the EGFR and induces rapid transient EGFR phosphorylation and subsequent activation of downstream signaling events such as mitogen-activated protein kinase (MAPK) phosphorylation, leading to the transcription of various genes. In parallel, HB-EGF-CTF is transported into the nucleus, where it subsequently induces nuclear export of PLZF, which leads to cell cycle progression. P indicates phosphorylation.
