ID
45676
Beskrivning
Principal Investigator: Irv L. Weissman, MD, Stanford University Medical School, Stanford, CA, USA MeSH: Breast Neoplasms https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001264 CD47 is a cell surface molecule that inhibits phagocytosis of cells that express it by binding to its receptor, SIRPα, on macrophages and other immune cells. CD47 is expressed at different levels in normal cells, however, in cancer cells, CD47 transcript and protein expression is aberrantly increased. Here we sought to uncover the regulators of *CD47* transcription, including active enhancers that increase its aberrant expression in cancer cells, in order to reveal mechanisms by which different neoplastic cells generate this dominant 'don't eat me' signal. Enhancers are genomic regions, often referred to as "switches", that can turn on or off the transcription of target genes. Recently the discovery of super-enhancers (SEs) has given more insight into the regulatory architecture of key genes that are highly expressed in a specific cell type, during a particular developmental stage or in disease. By analyzing the *CD47* regulatory genomic landscape, we discovered: i) A distinct super-enhancer (SE) is associated with *CD47* upregulation in breast cancer cells ii) Disruption of *CD47* SEs by using the BRD4 inhibitor JQ1 robustly reduces *CD47* gene expression; and iii) The TNF-NFKB1 signaling pathway is directly involved in the regulation of CD47 by interacting with a distal downstream constituent enhancer located within a *CD47*-associated SE specific to breast cancer. Our results describe a novel mechanism that cancer cells have evolved to drive CD47 overexpression to escape immune surveillance.
Länk
Nyckelord
Versioner (1)
- 2023-04-15 2023-04-15 - Simon Heim
Rättsinnehavare
Irv L. Weissman, MD, Stanford University Medical School, Stanford, CA, USA
Uppladdad den
15 april 2023
DOI
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Licens
Creative Commons BY 4.0
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dbGaP phs001264 A Super-Enhancer Associated with CD47 in Breast Cancer
The subject consent data table contains subject IDs, consent group information, subject aliases, and affection status of subjects for breast cancer.
- StudyEvent: SEV1
- The subject consent data table contains subject IDs, consent group information, subject aliases, and affection status of subjects for breast cancer.
- This subject sample mapping data table includes a mapping of study patient IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample aliases.
- This subject phenotype data table includes subjects' sex and age.
- This sample attributes table includes body site where sample was collected, analyte type, histological type, tumor status, primary tumor location, metastasis, stage, grade, treatment, genotyping center, and sequencing center.
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The subject consent data table contains subject IDs, consent group information, subject aliases, and affection status of subjects for breast cancer.
- StudyEvent: SEV1
- The subject consent data table contains subject IDs, consent group information, subject aliases, and affection status of subjects for breast cancer.
- This subject sample mapping data table includes a mapping of study patient IDs to sample IDs. Samples are the final preps submitted for genotyping, sequencing, and/or expression data. For example, if one patient (subject ID) gave one sample, and that sample was processed differently to generate 2 sequencing runs, there would be two rows, both using the same subject ID, but having 2 unique sample IDs. The data table also includes sample aliases.
- This subject phenotype data table includes subjects' sex and age.
- This sample attributes table includes body site where sample was collected, analyte type, histological type, tumor status, primary tumor location, metastasis, stage, grade, treatment, genotyping center, and sequencing center.
C0441833 (UMLS CUI [1,2])
C0242481 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,2])
C0681850 (UMLS CUI [1,3])
C3847505 (UMLS CUI [1,2])
C0449416 (UMLS CUI [1,3])