权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Single-Cell Misregulation of NRF2 in Basal-like Breast Cancer

基底样乳腺癌中 NRF2 的单细胞失调

基本信息

批准号：
9396814
负责人：
Elizabeth Pereira
金额：
$ 3.64万
依托单位：
UNIVERSITY OF VIRGINIA
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9396814
关键词：
Algorithms Alpha Cell Antioxidants Apoptosis Automobile Driving BRCA1 gene Behavior Bioinformatics Bioluminescence Breast Breast Cancer Cell Cancer cell line Cell Cycle Cell Survival Cells Complex Computer Simulation Data Development Drug Metabolic Detoxication Environment Epithelial Exhibits Gene Cluster Gene Expression Gene Targeting Genes Genetic Engineering Genetic Transcription Growth Heterogeneity Image Immunohistochemistry Injectable Lead Malignant - descriptor Malignant Neoplasms Malignant neoplasm of lung Mammary gland Messenger RNA Modeling Morphogenesis Mutation NF-E2-related factor 2 Oncogenes Oxidative Stress Pathway interactions Phenotype Play Population Pre-Clinical Model Process Proliferating Proliferation Marker Regulation Regulatory Pathway Research Role Route Shapes Staining method Stains Stress TP53 gene Testing The Cancer Genome Atlas Therapeutic Therapeutic Intervention Transcript Tumor Suppressor Genes Tumor Suppressor Proteins Tumorigenicity Up-Regulation Work Xenograft procedure actionable mutation anticancer research biological adaptation to stress breast tumorigenesis cancer cell cancer initiation carcinogenesis cell transformation chemotherapy in vivo inhibitor/antagonist knock-down loss of function mutation malignant breast neoplasm mammary epithelium mutant neoplastic cell programs stress tolerance therapeutic target three dimensional cell culture transcription factor transcriptome sequencing triple-negative invasive breast carcinoma tumor tumor progression tumorigenesis tumorigenic

项目摘要

Project Abstract Cancer is driven by a complex network of genes and pathways. Decades of research have discovered various oncogenes and tumor suppressors that can drive cell transformation and malignancy. However, there are many genes that are essential for cancer cell survival, but are not mutated themselves. These “non- oncogenes” can be involved in various cell-survival pathways such as the stress response, and might explain some of the heterogeneity observed among tumor cells that have the same driver mutations. How can we identify and target these genes to offer alternative routes to disarm and sensitize cancer cells to therapeutic interventions? One way to identify “non-oncogene” pathways is to evaluate how proliferating cells adjust to variable and evolving environments. By examining heterogeneous transcriptional regulatory states of single cells in a 3D culture model of breast epithelial organization, our lab discovered an important regulatory pathway that had a common upstream regulator, NRF2. NRF2 is a known oncogene in lung cancer, but mutations in the transcription factor are uncommon in breast cancer. In this proposal, I am studying the role of the non- oncogene, NRF2, in an aggressive subtype of breast cancer, in the hopes of determining new strategies to disrupt this non-oncogene addiction. This project entails three interrelated aims: 1) to determine the functional importance of NRF2 for growth, organization, and survival of triple-negative breast cancer cells; 2) to quantify and model the broader network context of NRF2 dynamics; 3) to test the impact of NRF2 on breast tumorigenesis in vivo. These aims are focused on the non-oncogene NRF2, which is classically known as an antioxidant transcription factor. Most cancer-related studies of NRF2 have focused on mutations in the transcription factor and the pathway associated with it. Our hypothesis is that there is another layer of NRF2- driven tumorigenesis that occurs on the single-cell level without mutation. A detailed understanding of NRF2 regulation could enable new strategies to disrupt this non-oncogene addiction and re-sensitize cancer cells to their environment and to chemotherapy.

项目摘要