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CUEDC1 is a primary target of ERα essential for the growth of breast cancer cells.

Research paper by Rui R Lopes, Gozde G Korkmaz, Sonia Aristin SA Revilla, Romy R van Vliet, Remco R Nagel, Lars L Custers, Yongsoo Y Kim, Pieter C PC van Breugel, Wilbert W Zwart, Behzad B Moumbeini, Zohar Z Manber, Ran R Elkon, Reuven R Agami

Indexed on: 27 Aug '18Published on: 27 Aug '18Published in: Cancer Letters



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. Published by Elsevier B.V.