Signal transduction to hypoxia-inducible factor 1.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that functions as a master regulator of O2 homeostasis. HIF-1 target genes encode proteins that increase O2 delivery and mediate adaptive responses to O2 deprivation. HIF-1 activity is regulated by the cellular O2 concentration and by the major growth factor-stimulated signal transduction pathways. In human cancer cells, both intratumoral hypoxia and genetic alterations affecting signal transduction pathways lead to increased HIF-1 activity, which promotes angiogenesis, metabolic adaptation, and other critical aspects of tumor progression.