Hypoxia‐inducible factor 1α (HIF‐1α) and HIF‐2α trigger HIF‐1 transcription to promote induction of various proangiogenic genes, such as VEGF, VEGFR, EGF, ANGPT, Tie‐2, TIMP‐1, and PAI‐1, and thereby play critical roles in tumor proliferation, apoptosis, metabolism, and metastasis in response to low‐oxygen concentrations in the TME, which can be hydrolysis by VHL protein.473. This evidence concerns the gene VHL and neoplasm.