Angiogenesis: how a tumor adapts to hypoxia.
The growth of new blood vessels from the preexisting vascular tree, also known as angiogenesis, occurs in situations such as wound and fracture healing, arthritis, cardiovascular and cerebral ischemia, and nearly every type of cancer known. Vascular endothelial growth factor (VEGF) has been shown to play a crucial role in these events. Hypoxia-dependent VEGF induction is mediated by hypoxia-inducible factor-1 (HIF-1). HIF-1 is a heterodimeric transcription factor tightly regulated by oxygen concentration. In this short review, we summarize recent data concerning the control of HIF-1 activity and notably the regulation of HIF-1alpha subunit by phosphorylation and the ubiquitin proteasomal degradation system. A complete knowledge of this mechanism could, by the design of new antiangiogenic strategies, have a strong impact in clinical oncology.
Richard
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Institute of Signaling, UMR CNRS 6543, Centre Antoine Lacassagne, 33 Avenue Valombrose, Nice Cedex, 06189, France.
Berra
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Pouysségur
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J
D000818:Animals; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D006868:Hydrolysis; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008025:Ligases; D008222:Lymphokines / Q000096:biosynthesis; D009389:Neovascularization, Pathologic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000502:physiology; D015398:Signal Transduction; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009687:Nuclear Proteins; D011506:Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases