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Effect of hypoxia and hypoxia inducible factor in breast cancer progression and mestastasis

Cristina Branco-Price

Appointment Period: 2011-2011 / Grant Years: [27] (Minority Supplement Slot)

Cristina Branco-PriceMy postdoctoral research project focused on the role of hypoxia-inducible factor (HIF) during breast cancer progression and mestastasis. This factor is not only the classic and all-encompassing factor in mammalian oxygen stress responses, but also negatively regulated via proteasomal degradation, which makes me feel very comfortable and familiar with its biology. 

Specifically, this project has lead to identifying the endothelial cell-specific HIF-1a as a promoting factor for breast cancer metastasis. I have found that endothelial cell-specific deletion of HIF-1a results in less tumor cell migration in vitro, and less lung metastasis in tumorbearing mice. In order to dissect the molecular mechanism underlying this phenomenon, thus far I have identified VEGF and iNOS, two HIF-1a targets as being involved in the regulation of endothelial permeability; VEGF-dependent activation of VEGFR2 results in endothelial permeability and it is apparent it does NOT promote both VEGF expression and VEGR2 activation since inhibition of iNOS in primary endothelial cells results in decreased VEGF signaling and VEGFR2 activation during hypoxia. 

Branco-Price C, Zhang N, Schnelle M, Evans C, Katschinski DM, Liao D, Ellies L, Johnson RS. Endothelial Cell HIF-1alpha and HIF-2alpha Differentially Regulate Metastatic Success. Cancer Cell. (2012) 21:52-65. PMID: 22264788.

NOTE: Candidate still in training in Johnson lab, but unfortunately Prof. Johnson was recently recruited to Cambridge University and moved there with lab (and Dr. Branco-Price) effective January, 2012.