Send to

Choose Destination
Cancer Biol Ther. 2006 May;5(5):476-9. Epub 2006 May 26.

Hypoxic microenvironment as a cradle for melanoma development and progression.

Author information

Gastroenterology Division, Department of Medicine, Abramson Cancer Center and Family Research Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.


Hypoxia-inducible factor (HIF)-1alpha, 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-1alpha 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, 8:443-54) 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-1alpha activity was found to be required in Akt-induced melanocyte transformation and tumor growth and it was suppressed greatly by mTOR inhibition with rapamycin. Since mTOR regulates HIF-1alpha 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-1alpha in the early stage of melanoma development and highlights the importance of the Akt-mTOR pathway in the regulation of HIF-1alpha.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Taylor & Francis
Loading ...
Support Center