EPAS1 and cancer: However, in CRC, HIFα can competitively bound to β-catenin to abolish the Tcf4/β-catenin complex, then enhancing the hypoxia tolerance of cancer cells to increase the survival in an anoxic environment.237 Interestingly, HIF2α binds to the β-catenin–Tcf complex at a different site from HIF1α to recruit p300 and then enhances Wnt/β-catenin signaling.210 The synergistic actions of HIF2α and β-catenin increase the proliferation of renal cell carcinoma cells.210 Accordingly, utilizing Tanshinone IIA can inhibit CRC angiogenesis by means of interrupting HIF-1α/β-catenin/Tcf3/Lef1 signaling.238,239