Zhao Lintao, Yang Yang, Yin Shigang, Yang Tao, Luo Jing, Xie Rongkai, Long Haixia, Jiang Lubin, Zhu Bo
Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
Institute of Cancer, PLA 324 Hospital, Chongqing, China.
Oncotarget. 2017 Jul 10;8(37):62217-62230. doi: 10.18632/oncotarget.19216. eCollection 2017 Sep 22.
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 , and . 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.
CCCTC结合因子(CTCF)通过表观遗传调控,根据癌症类型的不同,既发挥致癌作用,也发挥肿瘤抑制作用。表观遗传调控在癌症转移中起关键作用。我们的目标是研究CTCF在上皮性卵巢癌转移中是否起关键作用。首先,我们发现与非肿瘤组织相比,卵巢癌组织中CTCF的表达增加。CTCF表达增加预示着卵巢癌患者预后不良。此外,CTCF基因敲低显著抑制了卵巢癌细胞的转移,尽管它对细胞增殖和肿瘤生长没有影响。更重要的是,与来自同一卵巢癌患者的原发性肿瘤相比,转移灶中CTCF的表达更高。我们还证明CTCF影响许多与转移相关的基因,包括 、 和 。此外,我们的染色质免疫沉淀测序(ChIP-seq)结果显示这些基因有多个CTCF结合位点,染色质免疫沉淀聚合酶链反应(ChIP-PCR)进一步证实了这些结果。我们的结果表明,CTCF可能是通过干扰癌细胞转移来治疗卵巢癌的新型药物靶点。