1. CUEDC1 is a primary target of ERα essential for the growth of breast cancer cells.
- Author
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Lopes R, Korkmaz G, Revilla SA, van Vliet R, Nagel R, Custers L, Kim Y, van Breugel PC, Zwart W, Moumbeini B, Manber Z, Elkon R, and Agami R
- Subjects
- Breast Neoplasms metabolism, Breast Neoplasms pathology, CRISPR-Cas Systems, Cell Line, Tumor, Enhancer Elements, Genetic genetics, Estrogen Receptor alpha metabolism, Female, HEK293 Cells, Humans, Intracellular Signaling Peptides and Proteins metabolism, MCF-7 Cells, Breast Neoplasms genetics, Cell Proliferation genetics, Estrogen Receptor alpha genetics, Gene Expression Regulation, Neoplastic, Intracellular Signaling Peptides and Proteins genetics
- Abstract
Breast cancer is the most prevalent type of malignancy in women with ∼1.7 million new cases diagnosed annually, of which the majority express ERα (ESR1), a ligand-dependent transcription factor. Genome-wide chromatin binding maps suggest that ERα 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 ERα-positive breast cancer cell proliferation. We validated several candidates, including CUTE, a putative ERα-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 ERα-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 ERα in breast cancer. Thus, CUEDC1 is a functional target gene of ERα and is required for breast cancer cell proliferation., (Copyright © 2018 The Netherlands cancer Institute. Published by Elsevier B.V. All rights reserved.)
- Published
- 2018
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