Signal transduction to hypoxia-inducible factor 1

Hypoxia-inducible factor I (HIF-1) is a transcriptional activator that functions as a master regulator of O-2 homeostasis. HIF-1 target,genes encode proteins that increase O-2 delivery and mediate adaptive responses to O-2 deprivation. HIF-1 activity is regulated by the cellular O-2 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. (C) 2002 Elsevier Science Inc. All rights reserved.