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

基本信息

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
项目类别：
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

项目摘要

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.

概括该临床前转化提案的主要目标是确定成红细胞巨噬细胞的作用蛋白（Emp）在肿瘤进展中的作用，并确定其对结直肠癌的预后和预测价值 (CRC) 在我们已发表的初步研究中，我们发现 Emp 参与成红细胞。去核、巨噬细胞发育、细胞生长和分化、以及细胞粘附和迁移。此外，我们的初步免疫组织化学 (IHC) 通路是癌症进展的标志。对人类结直肠癌组织的评估表明，Emp 的表达在结直肠癌进展过程中不断增加。腺瘤到原发性腺癌到转移性癌因此，我们争论Emp是不是。为了检验这一假设，我们建议评估 Emp 相互作用的作用。带有粘附分子，用于附着到细胞外膜 (ECM)、用于分子串扰、用于效果这将通过三个目标来实现。将确定 Emp 与粘着斑内的 β1 整合素的相互作用及其参与肿瘤；Aim-2将验证Emp与肌动蛋白细胞骨架在ECM功能和转移；Aim-3 将确定 Emp 在 CRC 中的预后和预测价值。研究将表征 Emp 与 β1 整合素的分子相互作用，确定 Emp 对肌动蛋白细胞骨架和 ECM 的其他成分，识别有助于肿瘤进展，并评估 Emp 在 CRC 中的预测和预后价值。