Telmisartan Inhibits Cell Proliferation by Blocking Nuclear Translocation of ProHB-EGF C-Terminal Fragment in Colon Cancer Cells
Figure 1
Dual signaling pathways of EGFR phosphorylation and HB-EGF C-terminal fragment nuclear translocation during cell proliferation.
Quoted from [19] and modified. TPA induces an ADAM-mediated cleavage of proHB-EGF, and results in the ectodomain shedding of its N-terminal fragment and generation of an intracellular C-terminal fragment (CTF). The soluble HB-EGF binds to the EGFR and induces a rapid transient phosphorylation of EGFR. This phosphorylation results in the transcription of various genes. Meanwhile the HB-EGF-CTF is translocated into the nucleus, where it subsequently induces the nuclear export of PLZF. This results in the progression of cell cycle. The potent inhibitor blocks the nuclear translocation of HB-EGF-CTF. P indicates phosphorylation. Abbreviations: EGFR; epidermal growth factor receptor, TPA; 12-O-tetradecanoylphorbol-13-acetate, PKCδ; protein kinase Cδ, ADAM; a disintegrin and metalloproteinase, HB-EGF; heparin-binding EGF-like growth factor, CTF; C-terminal fragment, MAPK; mitogen-activated protein kinase, PLZF; promyelocytic leukemia zinc finger.