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Journal Club
Hypoxic Microenvironment as a Cradle for Melanoma Development and Progression
Carmen Z. Michaylira and Hiroshi Nakagawa
volume 5 | issue 5
May 2006Pages: 476-479
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Hypoxia-inducible factor (HIF)-1α, a global regulator of oxygen homeostasis, plays a crucial role in tumor cell adaptation to the hypoxic microenvironment through transcriptional regulation of its target genes. These genes in turn are involved in a plethora of biochemical as well as cell biological processes, including glucose metabolism, apoptosis, and angiogenesis. In melanoma, HIF-1α has been implicated in tumor progression with effects upon metastasis and angiogenesis. However, its role in malignant transformation by oncogenes has not been described. Bedogni et al. (Cancer Cell 2005, 8:443-454) report that the hypoxic microenvironment in the skin contributes to melanocyte transformation and tumor growth induced by oncogenes Ras and Akt, which are frequently activated in melanoma. HIF-1α activity was found to be required in Aktinduced melanocyte transformation and tumor growth and it was suppressed greatly by mTOR inhibition with rapamycin. Since mTOR regulates HIF-1α expression and its transcriptional activity, rapamycin was proposed as a promising hypoxia-related therapeutic approach in melanoma treatment. This study sheds light upon the role of HIF- 1α in the early stage of melanoma development and highlights the importance of the AktmTOR pathway in the regulation of HIF-1α.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.