EPAS1 and colorectal cancer: HIF-2α activates COX2/mPGES-1/PGE2 signaling to facilitate colon tumorigenesis.63 In addition, HIF-2α exerts its proliferative effects through modulating the EGFR, IGF1R and ERK/Akt signaling pathways in colorectal carcinoma, and its inhibition prevents growth and tumorigenesis of colorectal cancer in vivo.64 However, an opposite outcome was reported, with HIF-2α-selective knockdown having no effect on cellular proliferation in colorectal cells, although colony formation doubled in soft agar assays.28