Abstract
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.
MeSH terms
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Animals
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Ataxia Telangiectasia Mutated Proteins
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Cell Cycle Proteins / metabolism
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Humans
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Hypoxia / metabolism
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Hypoxia-Inducible Factor 1, alpha Subunit
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MAP Kinase Signaling System
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Neoplasms / physiopathology
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Neoplasms / therapy
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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Signal Transduction / physiology*
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Transcription Factors / metabolism*
Substances
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Cell Cycle Proteins
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Proto-Oncogene Proteins
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Transcription Factors
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ATR protein, human
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Ataxia Telangiectasia Mutated Proteins
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt