The Hypoxia-Inducible Factor-1α in Angiogenesis and Cancer: Insights from the Drosophila Model

Abstract

The hypoxia-inducible factor-1α (HIF-1α) is an evolutionarily conserved transcription factor with prominent roles in the hypoxic response, cell survival, angiogenesis and cancer. HIF-1α functions as a sensor of molecular oxygen: in the presence of oxygen, it is degraded by the proteasome, whereas in reduced oxygen tensions, it heterodimerizes with the constitutively expressed HIF-1b subunit forming the functional HIF1 transcription factor, which enters the nucleus to control expression of hypoxia-inducible genes. Since HIF-1α has been found upregulated in several cancers, it has attracted a lot of clinical interest, because it represents an interesting candidate for pharmacological chemotherapy interventions. In this chapter, we discuss our current knowledge on the HIF1 transcription factors and their major roles in development, physiology, angiogenesis and cancer using examples of recent studies in the model organism Drosophila melanogaster. Given the striking functional conservation between the mammalian and fruit fly HIF-1α, we expect that future studies in the Drosophila model will not only expand our knowledge on the basic HIF1 biology, but they will also pinpoint conserved molecular regulators of HIF1 that might lead to the discovery of novel cancer therapeutics.