CUEDC1 is a primary target of ER? essential for the growth of breast cancer cells.
Breast cancer is the most prevalent type of malignancy in women with ?1.7 million new cases diagnosed annually, of which the majority express ER? (ESR1), a ligand-dependent transcription factor. Genome-wide chromatin binding maps suggest that ER? may control the expression of thousands of genes, posing a great challenge in identifying ... functional targets. Recently, we developed a CRISPR-Cas9 functional genetic screening approach to identify enhancers required for ER?-positive breast cancer cell proliferation. We validated several candidates, including CUTE, a putative ER?-responsive enhancer located in the first intron of CUEDC1 (CUE-domain containing protein). Here, we show that CUTE controls CUEDC1 expression, and that this interaction is essential for ER?-mediated cell proliferation. Moreover, ectopic expression of CUEDC1, but not a CUE-domain mutant, rescues the defects in CUTE activity. Finally, CUEDC1 expression correlates positively with ER? in breast cancer. Thus, CUEDC1 is a functional target gene of ER? and is required for breast cancer cell proliferation.
Mesh Terms:
Breast Neoplasms, CRISPR-Cas Systems, Cell Line, Tumor, Cell Proliferation, Enhancer Elements, Genetic, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, MCF-7 Cells
Breast Neoplasms, CRISPR-Cas Systems, Cell Line, Tumor, Cell Proliferation, Enhancer Elements, Genetic, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins, MCF-7 Cells
Cancer Lett.
Date: Dec. 01, 2017
PubMed ID: 30145202
View in: Pubmed Google Scholar
Download Curated Data For This Publication
221587
Switch View:
- Interactions 1