J Cancer 2017; 8(11):2124-2131. doi:10.7150/jca.18818

Research Paper

Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53

Ji-Yeon Lee, Muhammad Mustafa†#, Clara Yuri Kim, Myoung Hee Kim

Department of Anatomy, Embryology Laboratory, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea
These authors contributed equally to this work.
#Current address: Department of Biological Sciences, Forman Christian College (A Chartered University), Ferozepur Road, Lahore 54600, Pakistan.

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Lee JY, Mustafa M, Kim CY, Kim MH. Depletion of CTCF in Breast Cancer Cells Selectively Induces Cancer Cell Death via p53. J Cancer 2017; 8(11):2124-2131. doi:10.7150/jca.18818. Available from http://www.jcancer.org/v08p2124.htm

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CCCTC-binding factor (CTCF), a ubiquitous 11-zinc finger multifunctional protein, has distinct molecular functions, such as transcriptional activation, repression, and chromatin barrier activity, in a locus-specific manner. Elevated CTCF levels in breast cancer cells are known to contribute to tumorigenesis; however, the underlying mechanism remains elusive. We investigated the effect of CTCF expression on breast cancer cell survival and elucidated its mechanism. CTCF depletion in MCF-7 cells led to a decreased cell growth and proliferation, surpassing the growth of normal cells under co-culture system of MCF-7-GFP and MCF10A. Here we propose that the phenotypes observed in CTCF-depleted MCF-7 cancer cells, such as reduced cell proliferation, increased apoptosis, and cell cycle arrest, are closely linked with the activation of p53. The consensus CTCF-binding site, located approximately 800 bp upstream of the first exon of TP53, was marked by H3K27me3, but not by the active mark H3K4me3, although CTCF is expressed. Knockdown of CTCF conversely led to the recruitment of H3K4me3 instead of H3K27me3, accompanying with the higher enrichment of PolII in the proximal promoter region of TP53. With the activation of p53, increased p21 and Bax expressions were observed in CTCF knockdown MCF-7 cells. Elucidating functional roles of CTCF and regulation mechanisms may help to guide CTCF and/or its related molecules as a therapeutic target to prevent cancer cell growth.

Keywords: CTCF, p53, breast cancer