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. 2017 Apr 27;8(24):38113–38135. doi: 10.18632/oncotarget.17494

Figure 9. A proposed model for IL-4/IL-13-induced NOX1 expression and colon cell proliferation.

Figure 9

IL-4/IL-13 bind to the Type II IL-4 receptor activating the JAK1/STAT6 signaling pathway, triggering GATA3 nuclear translocation that drives NOX1 expression. GATA3 binding to the NOX1 promoter initiates transcription that is dependent on serine phosphorylation (S308). Increased expression of full-length NOX1 (NOX1-L) promotes ROS production which can inhibit PTP activity and increase cyclin D3 levels, leading to enhanced cell cycle traverse through S-phase and increased colon cancer cell proliferation. Human colon cancers, when compared to adjacent uninvolved colonic epithelia, demonstrate significantly higher levels of NOX1 and IL-4Rα mRNA, consistent with this model.