CTCF promotes epithelial ovarian cancer metastasis by broadly controlling the expression of metastasis-associated genes
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Lintao Zhao1,4,*, Yang Yang1,*, Shigang Yin3,*, Tao Yang1, Jing Luo1, Rongkai Xie2, Haixia Long1, Lubin Jiang3 and Bo Zhu1
1Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China
2Department of Obstetrics and Gynecology, Xinqiao Hospital, Third Military Medical University, Chongqing, China
3Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
4Institute of Cancer, PLA 324 Hospital, Chongqing, China
*These authors have contributed equally to this work
Haixia Long, email: [email protected]
Lubin Jiang, email: [email protected]
Bo Zhu, email: [email protected]
Keywords: CTCF, metastasis, ovarian cancer, metastasis-associated genes, invasion
Received: February 12, 2017 Accepted: April 17, 2017 Published: July 10, 2017
CCCTC-binding factor (CTCF) functions as both an oncogenic and a tumor suppressor, depending on the cancer type, through epigenetic regulation. Epigenetic regulation plays a key role in cancer metastasis. Our objective was to investigate whether CTCF plays a crucial role in epithelial ovarian cancer metastasis. First, we found that CTCF expression was increased in ovarian cancer tissues compared to non-tumor tissues. Increased expression of CTCF predicts poor prognosis of ovarian cancer patients. In addition, CTCF knockdown significantly inhibited the metastasis of ovarian cancer cells, although it had no effect on cell proliferation and tumor growth. More importantly, CTCF expression was higher in metastatic lesions compared to primary tumors from the same ovarian cancer patients. We also demonstrated that CTCF affects a number of metastasis-associated genes, including CTBP1, SERPINE1 and SRC. Additionally, our ChIP-seq results revealed that these genes have multiple CTCF-binding sites, findings that were further confirmed by ChIP-PCR. Our results suggest that CTCF could be a novel drug target to treat ovarian cancer by interfering with cancer cell metastasis.
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