The most important clinical factor associated with poor survival during breast cancer progression is the appearance of metastasis. It is such secondary tumor sites, often far away from the initial breast tumor, that threaten the life of afflicted women. Our research program aims at uncovering the molecular mechanisms that facilitate both the escape of cancer cells from the breast tumor and their ability to enter blood vessels to ultimately travel to secondary tumor soil where they can grow as metastasis. Dr. Côté and his team focus on a protein named AXL that is found at the surface of both the cancer cells and the tumor blood vessels. The presence of AXL in human breast tumors correlates with the formation of metastases. Here, they propose to study how AXL is working in both the tumor cells, to promote their motility, and in the blood vessels, to facilitate the seeding of the tumor cells at distant sites. To achieve these objectives, they will use engineered mice that recapitulate human breast cancer in addition to cell culture models to study cell movement and blood vessel integrity.

Understanding the intracellular mechanisms by which growth factors produce their effects in endothelial cells is an important aspect of vascular biology. Endothelial cell are intimately involved in formation of new blood vessel, termed angiogenesis, and in the control of vascular tone. Vascular endothelial growth factor ( VEGF ) is an important factor for endothelial cells as it promotes their proliferation, survival and angiogenesis. Angiogenesis is deregulated in several cardiovascular pathologies such as atherosclerosis and cardiac infarct. In this proposal, we will attempt to modulate the ability of VEGF to control angiogenesis by altering cellular processes that affect the degradation and stability of VEGF receptors in endothelial cells. Furthermore, we will investigate how the release of nitric oxide, a critical factor produced by endothelial cells in response to VEGF, is affected by the modulation of VEGF receptor degradation.

Defining new approaches to modulate the effects of an essential factor for the formation and maintenance of blood vessels will hopefully open the way to the identification of novel therapeutic targets in cardiac and vascular diseases.

Organisation du Colloque Signalisation Québec 2012, 13 au 15 juin 2012.

Programme scientifique