Hypoxia-inducible factor-1 in tumour angiogenesis

Hypoxia-inducible factor-1 (HIF-1), composed of HIF-alpha and HIF-beta subunits, is a heterodimeric transcriptional activator. In response to hypoxia, stimulation of growth factors, and activation of oncogenes as well as carcinogens, HIF-1 alpha is overexpressed and/or activated and targets those genes which are required for angiogenesis, metabolic adaptation to low oxygen and promotes survival. HIF-1 is critical for both physiological and pathological processes. Several dozens of putative direct HIF-1 target genes have been identified on the basis of one or more cis-acting hypoxia-response elements that contain an HIF-1 binding site. A variety of regulators including growth factors, genetic alterations, stress activators, and some carcinogens have been documented for regulation of HIF-1 in which several signaling pathways are involved depending on the stimuli and cell types. Activation of HIF-1 in combination with activated signaling pathways and regulators is implicated in tumour progression and prognosis. This review presents a summary of the structure and function of HIF-1 alpha, and correlation among specific regulators and their signaling pathways.