Hypoxia-inducible factors, stem cells, and cancer.
Regions of severe oxygen deprivation (hypoxia) arise in tumors due to rapid cell division and aberrant blood vessel formation. The hypoxia-inducible factors (HIFs) mediate transcriptional responses to localized hypoxia in normal tissues and in cancers and can promote tumor progression by altering cellular metabolism and stimulating angiogenesis. Recently, HIFs have been shown to activate specific signaling pathways such as Notch and the expression of transcription factors such as Oct4 that control stem cell self renewal and multipotency. As many cancers are thought to develop from a small number of transformed, self-renewing, and multipotent "cancer stem cells," these results suggest new roles for HIFs in tumor progression.
Keith
Brian
B
Abramson Family Cancer Research Institute, University of Pennsylvania, 453 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA. bkeith@mail.med.upenn.edu <bkeith@mail.med.upenn.edu>
Simon
M Celeste
MC
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D015687:Cell Hypoxia; D018450:Disease Progression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins