The Role of Spingolipid- and Cholesterol-Rich Membrane Domains in Pathophysiology of Cultured Human Breast Cancer
Annual rept. 15 May 2000-14 May 2001
STATE UNIV OF NEW YORK AT STONY BROOK
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UPAR urokinase-type plasminogen activator receptor is a key player in metastasis of breast cancer cells. We suggest that uPAR, because it is a GPI-anchored protein, must be present in discrete subregions or rafts in the cell surface to function. Our proposal has two parts. First, we will set up systems in our lab for studying signaling through uPAR in cultured human breast cancer cells. Second, we will disrupt rafts, and determine whether signal transduction is affected. Our most important advances this year have been in characterizing lipid rafts, and in determining specific experimental protocols necessary for disrupting them. We have also started to make some headway in characterizing signaling pathways Yes, MAP kinase in which rafts are involved. With this foundation laid, the most important focus of the next year will be to improve procedures for examining uPA and uPAR in rafts. It is clear that uPA interactions with uPAR play a key role in metastasis, the deadliest feature of breast cancer. Our findings strongly suggest that the presence of uPAR, a GPI-anchored protein, in membrane rafts affects its signaling and its ability to govern cell migration during metastasis. The need to control this signaling pathway has never been greater.
- Anatomy and Physiology
- Medicine and Medical Research