Project 1: 2/2 The Alabama State University/UAB Comprehensive cancer Center partnership

项目 1：2/2 阿拉巴马州立大学/UAB 综合癌症中心合作伙伴关系

• 批准号: 8849688
• 负责人: Shivani Soni
• 金额: $ 5.31万
• 依托单位: ALABAMA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8849688
• 关键词: Abnormal Erythroblast; Actins; Adenocarcinoma; Adhesions; Aggressive behavior; Alabama; Binding; Cell Adhesion Molecules; Cell Differentiation process; Cell Proliferation; Cell Shape; Cell division; Cell membrane; Cell-Cell Adhesion; Cells; Characteristics; Clinical; Clinical Research; Collaborations; Colorectal Cancer; Communities; Comprehensive Cancer Center; Cytoskeleton; Data; Development; Differentiation and Growth; Disease; Embryonic Development; Erythroblasts; Erythroid; Evaluation; Extracellular Matrix; Focal Adhesions; Gene Proteins; Gene Targeting; Goals; Homeostasis; Human; Immunologic Surveillance; Integrins; Laboratories; Lead; Lesion; Link; Malignant - descriptor; Malignant Neoplasms; Manuscripts; Membrane; Mentors; Mentorship; Metastatic Carcinoma; Minority-Serving Institution; Molecular; Molecular Target; Neoplasm Metastasis; Nuclear Matrix; Organism; Outcome; Pathologic; Pathway interactions; Phagocytosis; Population Heterogeneity; Predictive Value; Premalignant; Process; Proteins; Publishing; Recurrence; Research; Research Personnel; Research Training; Role; Signal Pathway; Signal Transduction; Staging; Technology; Testing; Tissues; Training and Education; Treatment Efficacy; Universities; University of Alabama at Birmingham Cancer Center; Vision; Wound Healing; adenoma; anticancer research; base; cancer health disparity; career; cell growth; cell motility; directional cell; experience; extracellular; macrophage; metastatic colorectal; migration; monocyte; peripheral blood; pre-clinical; preclinical study; prognostic; protein complex; racial and ethnic; research study; therapeutic target; translational study; tumor; tumor microenvironment; tumor progression

SUMMARY The primary goal of this preclinical translational proposal is to determine the role of erythroblast macrophage protein (Emp) in tumor progression and to establish its prognostic and predictive value for colorectal cancers (CRCs). In our published and preliminary studies, we have discovered that Emp is involved in erythroblast enucleation, macrophage development, cell growth and differentiation, and cell adhesion and migration. These pathways are hallmarks of cancer progression. Additionally, our preliminary immunohistochemical (IHC) evaluations of human CRC tissues have demonstrated increasing expression of Emp in progression of adenomas to primary adenocarcinomas to metastatic carcinomas. Therefore, we hypothesize that Emp is involved in CRC progression. To test this hypothesis, we propose to evaluate the role of Emp interactions with adhesion molecules for attachment to extracellular membranes (ECM), for molecular cross-talk, for effects on the tumor microenvironment, and for progression of CRCs. This will be accomplished in three aims. Aim-1 will determine the interaction of Emp with β1 integrin within focal adhesion plaques and its involvement in tumor progression; Aim-2 will verify the interaction of Emp with the actin cytoskeleton in ECM functions and in metastasis; and Aim-3 will establish the prognostic and predictive value of Emp in CRCs. The proposed studies will characterize the molecular interactions of Emp with β1 integrin, ascertain the effects of Emp on the actin cytoskeleton and other components of the ECM, identify new molecular determinants that contribute to tumor progression, and assess the predictive and prognostic value of Emp in CRCs.

概括 此临床前翻译建议的主要目标是确定红细胞巨噬细胞的作用 肿瘤进展中的蛋白质（EMP），并为结直肠癌建立其预后和预测价值 （CRC）。在我们发表的初步研究中，我们发现EMP参与了红细胞 枚举，巨噬细胞发育，细胞生长和分化以及细胞粘合剂和迁移。这些 途径是癌症进展的标志。此外，我们的初步免疫组织化学（IHC） 对人CRC组织的评估表明，EMP在进展中的表达增加 腺瘤至原发性腺癌对转移性癌。因此，我们假设EMP是 参与CRC的进展。为了检验这一假设，我们建议评估EMP相互作用的作用 与粘合分子相结合到细胞外膜（ECM），用于分子串扰，以效应 在肿瘤微环境和CRC的发展上。这将在三个目标中实现。 AIM-1 将确定EMP与β1整联蛋白在粘着斑斑块中的相互作用及其参与 肿瘤进展； AIM-2将验证EMP与ECM功能中肌动蛋白细胞骨架的相互作用 转移; AIM-3将建立CRC中EMP的预后和预测价值。提议 研究将表征EMP与β1整合素的分子相互作用，确定EMP对 ECM的肌动蛋白细胞骨架和其他成分，确定有助于 肿瘤进展，并评估CRC中EMP的预测和预后价值。