Grant: Operating Grant

The most important clinical factor associated with poor survival during breast cancer progression is the appearance of metastases. It is such secondary tumors, 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. We focus here 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, we first study the progression of breast cancer in a mouse model of breast cancer where AXL is deleted. Second, we use sophisticated protein analyses methods to detect the large number of proteins engaged by AXL to promote cell invasion. The function of the modulated proteins will be analyzed in molecular details. Finally, we used gene signatures of aggressive cancer cells lacking AXL expression to identify candidate anti-metastatic drugs that we will test in vitro and in vivo. Globally, this project aims to develop strategies to interfere with AXL function in metastatic breast cancer cells with the ultimate objective of moving toward the identification of anti-metastatic strategies.