GLYCOSPHINGOLIPID ENRICHED MICRODOMAINS IN CANCER CELL INVASION

鞘糖脂富集癌细胞侵袭中的微结构域

• 批准号: 7960230
• 负责人: WIM Floris Albert STEELANT
• 金额: $ 12.87万
• 依托单位: NEW MEXICO STATE UNIVERSITY LAS CRUCES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7960230
• 关键词: Antigens; Behavior; Biological Process; Biomedical Research; Breast; Breast Cancer Cell; Cell Adhesion; Cell Adhesion Molecules; Cell membrane; Cell-Cell Adhesion; Colon Carcinoma; Complex; Computer Retrieval of Information on Scientific Projects Database; Disease; Ethers; Funding; Glycosphingolipids; Goals; Grant; Human; Institution; Integrin alpha1; Lipids; Location; MCF7 cell; Malignant Neoplasms; Mediator of activation protein; Membrane Microdomains; Membrane Proteins; Molecular Probes; New Mexico; Peptide Hydrolases; Phosphorylcholine; Process; Proteins; Research; Research Personnel; Resources; Signal Pathway; Signal Transduction; Signaling Molecule; Source; Transducers; Tumor Cell Invasion; United States National Institutes of Health; analog; cancer cell; tumor

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. Glycosphingolipid Enriched Microdomains in Cancer Cell Invasion The ultimate goal of this study was to investigate biological processes involving Glycosphingolipid Enriched Microdomains (GEM) and their implication in diseases, such as cancer. Cancer cell invasion is a highly complex and multistep process, that is characterized by altered expression levels of cell adhesion molecules and secretion of proteolytic enzymes, along with changes in expression or activities of a variety of cellular proteins in multiple branching signaling pathways. In addition, the plasma membrane contains membrane microdomains enriched in tumor-associated glycosphingolipid (GSL)-antigens that function as mediators of cell adhesion, and in signaling molecules, providing important locations for cell signaling. Recent studies showed that tumor cell invasion often results from aberrant signaling mechanisms initiated by differential organization and clustering of GSLs and/or membrane proteins, and their assembly with signaling molecules. The synthetic ether lipid analog ET-18-OMe (1-O-octadecyl-2-O-methyl-glycero-3-phosphocholine) was previously shown to influence invasion of human breast and colon cancer cells and is used as a molecular probe to induce cellular invasion in order to explore changes in composition, translocation and organization of crucial molecules and the possible involvement of membrane microdomains. Our results show that reorganization, clustering and assembly of specific membrane proteins and signal transducers with glycosphingolipids in membrane microdomains are responsible for loss of cell-cell adhesion and subsequent result in increased invasiveness of MCF-7 breast cancer cells. In contrast, the invasive behavior of HCT-8 colon cancer cells was initiated through clustering of integrin alpha1 subunits and the activation of associated FAK/cSrc complexes.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 癌细胞侵袭中富含鞘糖脂的微结构域 这项研究的最终目标是研究涉及富含鞘糖脂微域 (GEM) 的生物过程及其对癌症等疾病的影响。癌细胞侵袭是一个高度复杂的多步骤过程，其特征是细胞粘附分子的表达水平和蛋白水解酶的分泌改变，以及多个分支信号通路中多种细胞蛋白的表达或活性的变化。此外，质膜含有富含肿瘤相关鞘糖脂 (GSL) 抗原和信号分子的膜微结构域，这些抗原充当细胞粘附的介质，为细胞信号传导提供重要位置。最近的研究表明，肿瘤细胞侵袭通常是由 GSL 和/或膜蛋白的差异组织和聚集及其与信号分子的组装引发的异常信号传导机制引起的。合成醚脂质类似物 ET-18-OMe（1-O-十八烷基-2-O-甲基-甘油-3-磷酸胆碱）先前已被证明可以影响人类乳腺癌和结肠癌细胞的侵袭，并用作分子探针诱导细胞侵袭，以探索关键分子的组成、易位和组织的变化以及膜微区的可能参与。 我们的结果表明，膜微区中特定膜蛋白和鞘糖脂信号转导器的重组、聚集和组装是导致细胞间粘附丧失并随后导致 MCF-7 乳腺癌细胞侵袭性增加的原因。相比之下，HCT-8结肠癌细胞的侵袭行为是通过整合素α1亚基的聚集和相关FAK/cSrc复合物的激活来启动的。