GLYCOSPHINGOLIPID ENRICHED MICRODOMAINS IN CANCER CELL INVASION

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。本研究的最终目的是研究鞘糖脂富集微域（GEM）的生物学过程及其在癌症等疾病中的意义。了解肿瘤细胞的转移和侵袭特性对肿瘤的恶性研究至关重要。肿瘤细胞的恶性可以通过GEM中肿瘤相关鞘糖脂（GSL）抗原的组织来表征，因为它们参与肿瘤细胞的粘附和信号转导。最近的研究表明，单胞嘧啶- gb5是GEM中的一个全球系列结构，与证监会和Fak组织在一起，是MCF-7人乳腺癌细胞侵袭特性的基础。ET-18-OMe （1- o-十八烷基-2- o-甲基-甘油-3-磷酸胆碱）是一类很有前途的新型癌症化疗药物。我们之前表明ET-18-OMe能够影响MCF-7细胞的侵袭。由于侵袭是恶性肿瘤的标志，任何揭示的机制都将为抗肿瘤治疗的新策略开辟可能性。因此，我们在ET-18-OMe诱导侵袭的机制中，研究了信号分子和膜受体参与的GEM组成和易位的变化。在第一年（2004年7月1日至2005年6月30日），我们能够解开证监会和FAK在ET-18-OMe诱导入侵中的参与。此外，我们发现证监会在ET-18-OMe治疗后与GEM组织。我们的研究结果表明GEM和相关的信号转导分子在ET-18-OMe诱导的侵袭机制中起着关键作用。

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.