Hypoxia inducible factor-2α: a critical mediator of aggressive tumor phenotypes

Intra-tumoral hypoxia (low oxygen [O-2] level) is an independent indicator of unfavorable patient diagnosis, and increasing evidence demonstrates that hypoxia contributes to a more aggressive tumor phenotype. Adaptation to hypoxia is predominantly regulated by two structurally related hypoxia inducible factors, HIF-1 alpha and HIF-2 alpha, which activate the expression of genes involved in proliferation, metabolism, angiogenesis, and metastasis. While highly homologous, HIF-1 alpha and HIF-2 alpha have been shown to have different roles in tumorigenesis dependent on specific tumor microenvironments. Here we summarize recent studies on HIF-2 alpha and discuss the potential mechanisms whereby it contributes to tumor aggressiveness.