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Full Project 1: LSR Alters Metabolic Signaling to Drive Aggressive Breast Cancer Behaviors

完整项目 1：LSR 改变代谢信号以驱动侵袭性乳腺癌行为

基本信息

批准号：
10247134
负责人：
Keith Burridge
金额：
$ 3.11万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-28 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10247134
关键词：
Address Affect African American Aggressive behavior Anabolism Behavior Binding Bioenergetics Biological Biological Assay Biological Factors Breast Breast Cancer Cell Cancerous Caucasians Cell division Cell physiology Cells Characteristics Cholesterol Chronic Clinical Collaborations Cytoplasmic Tail Data Data Set Diagnosis Diet Disease Distant Metastasis Endocytosis Energy-Generating Resources Environment Etiology Event Fatty acid glycerol esters Gene Chips Gene Expression Genes Genetic Transcription Glycogen Goals Guanosine Triphosphate Phosphohydrolases Hepatic High Fat Diet Hospitals In Vitro Incidence Lead Leptin Lesion Link Lipids Lipolysis Lipoprotein Receptor Lipoproteins Malignant - descriptor Malignant Neoplasms Mammary Gland Parenchyma Mammary Neoplasms Measures Mediating Membrane Membrane Lipids Metabolic Metabolic syndrome Metabolism Molecular Mus Neoplasm Metastasis Nuclear Obesity Observational Study Outcome Pathway Analysis Pathway interactions Patient-Focused Outcomes Patients Phenotype Phosphoproteins Predisposition Prevalence Property Proteins Proteomics Publishing Race Recurrence Regulation Research Resistance Resources Role Signal Pathway Signal Transduction Signaling Molecule Site Statistical Models Testing Tight Junctions Tumor Subtype Variant Woman Work Xenograft procedure anticancer research cancer health disparity cancer stem cell cancer subtypes cell behavior effective therapy epidemiology study ethnic diversity experimental study glucose uptake health disparity improved in vivo insight lipid metabolism lipid transport malignant breast neoplasm metabolomics mortality new therapeutic target novel novel strategies obesogenic overexpression racial disparity receptor expression receptor function response rho rho GTP-Binding Proteins stem stem-like cell therapeutic development tumor tumor behavior tumor microenvironment tumor progression tumorigenesis tumorigenic uptake

项目摘要

Project Summary/Abstract African American (AA) women have higher breast cancer mortality rates compared to other races. A greater prevalence of basal-like breast cancers in AA women explain some disparities, as these tumors are clinically the most aggressive, characterized by cancer stem No effective therapies exist and cell features. survival is poor. Escalating this disparity is the disease promoting effects of obesity, which is significantly higher in AA. The majority of studies on breast cancer disparities examine tumor characteristics, but the etiologic factors that lead to this disparity remain undefined. Our primary objective is to identify the mechanisms involved in promoting aggressive breast cancer in AAs, as a consequence of stromal effects at the site of the cancerous lesion. A key molecular pathway has been identified which integrates these clinical, microenvironmental and biological factors to affect tumor behavior. Aim 1 takes a novel approach, combining our published proteomic and gene expression datasets detailing race and tumor-subtype specific stromal interactions with our recently published data on the identified pathway promoting cancer stem cell- like, aggressive behaviors. Aims 2 and 3 extend these data to experimental studies to elucidate mechanistic details. To accomplish these tasks, our team established research partnerships that provides access to resources including the Normal Breast Study: a unique epidemiologic study from ethnically diverse patients at UNC Hospitals. There are several important biological implications of this work. The observation that AA breast tissue is enriched with distinct proteins, the prevalence of obesity in AA, and the predisposition to develop basal-like tumors strongly suggests a biological link between race, metabolism and cancer subtype. The role of differentially regulated metabolic-sensitive proteins in the tumor microenvironment will provide novel insights into the biological basis of racial disparities. The long-term goal of our collaboration is to understand tumor-microenvironment interactions and their influence on breast cancer disparities. Our distinctive approach will expose unique characteristics of the breast tissue microenvironment and will integrate advances in the field of tumor microenvironment with health disparities research. Relevance This proposal addresses breast cancer disparities by studying a key pathway that drive the aggressiveness of breast cancers. By combining observational studies on differences in this pathway by race, BMI, and breast cancer subtype with experimental studies to understand the role of this pathway in cellular phenotypes, this project will provide important and novel insight into the biological basis of racial disparities.

项目总结/文摘