Met (HGF Receptor) in Breast Cancer
Annual summary rept. 1 Sep 2009-31 Aug 2010
YALE UNIV NEW HAVEN CT
Pagination or Media Count:
The hepatocyte growth factor HGFMet signaling pathway has been shown to be important for stimulating cell proliferation, motility, invasion and metastasis. Recent work from our lab has identified a 60 kDa fragment from the carboxy-terminal domain of Met that localizes to the nucleus. Preliminary data from our also indicates that Met is translocated to the nucleus during in vitro wound healing of epithelial sheets of cells, but appears to be antibody dependent as a newly validated mouse monoclonal antibody does not detect the 60 kDa fragment. Because several pharmaceutical companies are currently developing Met-based therapies, it becomes even more important to gain an understanding of the role of nuclear Met, especially whether or not it may be contributing to invasion and metastasis. To date, no studies have been conducted to understand this aspect of Met function. Therefore the objectives of my proposal are to assess the role of Met in a model of epithelial-mesenchymal transition EMT, identify key residues in the Met receptor necessary for nuclear translocation, and determine the functional role of Met in the nucleus.
- Medicine and Medical Research