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

Rui Lopes, Gozde Korkmaz, Sonia Aristin Revilla, Romy van Vliet, Remco Nagel, Lars Custers, Yongsoo Kim, Pieter C. van Breugel, Wilbert Zwart, Behzad Moumbeini, Zohar Manber, Ran Elkon, Reuven Agami*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)87-95
Number of pages9
JournalCancer Letters
Volume436
DOIs
Publication statusPublished - 1 Nov 2018

Cite this

Lopes, R., Korkmaz, G., Revilla, S. A., van Vliet, R., Nagel, R., Custers, L., ... Agami, R. (2018). CUEDC1 is a primary target of ERα essential for the growth of breast cancer cells. Cancer Letters, 436, 87-95. https://doi.org/10.1016/j.canlet.2018.08.018