CCCTC-binding factor inhibits breast cancer cell proliferation and metastasis via inactivation of the nuclear factor-kappaB pathway
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Jie Wu1,*, Peng-Chang Li1,*, Jun-Yi Pang2, Guo-You Liu3, Xue-Min Xie3, Jia-Yao Li1, Yi-Cong Yin1, Jian-Hua Han1, Xiu-Zhi Guo1 and Ling Qiu1
1Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China
2Department of Pathology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Science, Beijing, 100730, China
3State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100005, China
*These authors contributed equally to this work
Ling Qiu, email: firstname.lastname@example.org
Keywords: CCCTC-binding factor, breast cancer, proliferation, metastasis, nuclear factor-kappaB
Received: December 01, 2016 Accepted: June 18, 2017 Published: July 04, 2017
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues. In addition, CTCF expression correlated significantly with cancer stage (P = 0.043) and pathological differentiation (P = 0.029). Furthermore, CTCF overexpression resulted in the inhibition of proliferation, migration, and invasion, while CTCF knockdown induced these processes in breast cancer cells. Transcriptome analysis and further experimental confirmation in MDA-MD-231 cells revealed that forced overexpression of CTCF might attenuate the DNA-binding ability of nuclear factor-kappaB (NF-κB) p65 subunit and inhibit activation of NF-κB and its target pro-oncogenes (tumor necrosis factor alpha-induced protein 3 [TNFAIP3]) and genes for growth-related proteins (early growth response protein 1 [EGR1] and growth arrest and DNA-damage-inducible alpha [GADD45a]). The present study provides a new insight into the tumor suppressor roles of CTCF in breast cancer development and suggests that the CTCF/NF-κB pathway is a potential target for breast cancer therapy.
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