TY - JOUR
T1 - CUEDC1 is a primary target of ERα essential for the growth of breast cancer cells
AU - Lopes, Rui
AU - Korkmaz, Gozde
AU - Revilla, Sonia Aristin
AU - van Vliet, Romy
AU - Nagel, Remco
AU - Custers, Lars
AU - Kim, Yongsoo
AU - van Breugel, Pieter C.
AU - Zwart, Wilbert
AU - Moumbeini, Behzad
AU - Manber, Zohar
AU - Elkon, Ran
AU - Agami, Reuven
N1 - Publisher Copyright:
© 2018 The Netherlands cancer Institute
PY - 2018/11/1
Y1 - 2018/11/1
N2 - 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.
AB - 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.
KW - Breast
KW - CRISPR-Cas9
KW - Cancer
KW - Enhancer
UR - http://www.scopus.com/inward/record.url?scp=85052313276&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2018.08.018
DO - 10.1016/j.canlet.2018.08.018
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C2 - 30145202
AN - SCOPUS:85052313276
SN - 0304-3835
VL - 436
SP - 87
EP - 95
JO - Cancer Letters
JF - Cancer Letters
ER -