Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10895628 | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer | 2011 | 12 Pages |
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.
Keywords
phosphatidyl inositol-3 kinaseSBCHREBcl-xLBCL2/adenovirus E1B 19 kDa protein-interacting protein 3BNIP3PHDMITFSPRY2CMMCBPHIF-1αCPDsNDRG1BCCBcl-2mTORHIF-1UVBMEFSIAH2SCCSELENBP1PI3KMAPKROSUltravioletBaxApoptosisCyclobutane pyrimidine dimersSkin cancerCarcinogenesissunburn cellhypoxia inducible factor 1hypoxia response elementVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)Microphthalmia-associated transcription factorB cell lymphomaB-cell lymphoma-extra largemelanocytesCutaneous malignant melanomamammalian target of rapamycinBcl-2-associated X proteinmitogen activated protein kinaseProlyl hydroxylaseBasal cell carcinomaSquamous cell carcinomaKeratinocytesReactive oxygen species
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Authors
Kris Nys, Hannelore Maes, Aleksandra Maria Dudek, Patrizia Agostinis,