The role of hypoxia-inducible factor-2 in digestive system cancers

Hypoxia is an all but ubiquitous phenomenon in cancers. Two known hypoxia-inducible factors (HIFs), HIF-1 alpha and HIF-2 alpha, primarily mediate the transcriptional response to hypoxia. Despite the high homology between HIF-1 alpha and HIF-2 alpha, emerging evidence suggests differences between both molecules in terms of transcriptional targets as well as impact on multiple physiological pathways and tumorigenesis. To date, much progress has been made toward understanding the roles of HIF-2 alpha in digestive system cancers. Indeed, HIF-2 alpha has been shown to regulate multiple aspects of digestive system cancers, including cell proliferation, angiogenesis and apoptosis, metabolism, metastasis and resistance to chemotherapy. These findings make HIF-2 alpha a critical regulator of this malignant phenotype. Here we summarize the function of HIF-2 during cancer development as well as its contribution to tumorigenesis in digestive system malignancies.