GLYCOSPHINGOLIPID ENRICHED MICRODOMAINS IN CANCER CELL INVASION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ultimate goal of this study is to investigate biological processes involving Glycosphingolipid Enriched Microdomains (GEM) and their implication in diseases, such as cancer. Understanding metastatic and invasive properties of tumor cells is crucial for the investigation of tumor malignancy. Tumor cell malignancy can be characterized by organization of tumor-associated glycosphingolipid (GSL)-antigens in GEM, since they are involved in tumor cell adhesion and signal transduction. Recent studies have shown that monosialyl-Gb5, a globo-series structure in GEM, organized with cSrc and Fak underlies the invasive properties of MCF-7 human breast cancer cells. ET-18-OMe (1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine), belongs to a novel class of promising cancer chemotherapeutic drugs. We previously showed that ET-18-OMe is able to influence invasion in MCF-7 cells. Since invasion is the hallmark for cancer malignancy, any mechanism revealed will open possibilities for new strategies in anti-tumor treatment. We therefore investigate the change in composition and translocation of GEM with the involvement of signaling molecules and membrane receptors in the mechanism underlying ET-18-OMe induced invasion. In the first year (7/1/2004 - 6/30/2005) we were able to unravel the involvement of cSrc and FAK in ET-18-OMe induced invasion. In addition we found that cSrc is organized with GEM upon ET-18-OMe treatment. Our findings indicate a pivotal role of GEM and associated signal transduction molecules in the mechanism of ET-18-OMe induced invasion.