title: Uncovering the role of hypoxia inducible factor-1α in skin carcinogenesis.
abstract: The hypoxia inducible factor-1α (HIF-1α) is a pleiotropic transcription factor typically activated in response to low oxygen tension as well as other stress factors in normoxic conditions. Upon activation HIF-1α mediates the transcriptional activation of target genes involved in a variety of processes comprising stress adaptation, metabolism, growth and invasion, but also apoptotic cell death. The molecular mechanisms, signaling pathways and downstream targets evoked by the activation of HIF-1α in epidermal cells are becoming increasingly understood and underscore the participation of HIF-1α in crucial processes including malignant transformation and cancer progression. Recent studies have implicated HIF-1α as an integral part of the multifaceted signal transduction initiated by the exposure of keratinocytes to ultraviolet radiation B (UVB), which represents the most ubiquitous hazard for human skin and the principal risk factor for skin cancer. HIF-1α activation by UVB exposure contributes to either repair or the removal of UVB-damaged keratinocytes by inducing apoptosis, thus revealing a tumor suppressor role for HIF-1α in these cells. On the other hand, the constitutive expression of HIF-1α evoked by the mild hypoxic state of the skin has been implicated as a positive factor in the transformation of normal melanocytes into malignant melanoma, one of the most aggressive types of human cancers. Here we review the uncovered and complex role of HIF-1α in skin carcinogenesis.
authors.affiliation: Cell Death Research & Therapy Laboratory, Department Molecular and Cell Biology, Faculty of Medicine, Catholic University of Leuven, Herestroat 49, box 901, B-3000, Belgium.
authors.forename: Kris
authors.initials: K
authors.lastname: Nys
authors.forename: Hannelore
authors.initials: H
authors.lastname: Maes
authors.forename: Aleksandra Maria
authors.initials: AM
authors.lastname: Dudek
authors.forename: Patrizia
authors.initials: P
authors.lastname: Agostinis
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D012867:Skin / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology*; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit