ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.
ELF3 is a negative regulator of epithelial-mesenchymal transition in ovarian cancer cells.
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DOI：
10.18632/oncotarget.15208
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发表时间：
2017-03-07
期刊：
影响因子：
--
通讯作者：
Mok SC
中科院分区：
文献类型：
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作者：
Yeung TL;Leung CS;Wong KK;Gutierrez-Hartmann A;Kwong J;Gershenson DM;Mok SC
转录因子是各种生物化学途径的主开关。然而，参与卵巢癌发病机制的转录因子还有待深入研究。因此，在本研究中，我们评估了转录因子E74样因子3（ELF 3）的预后价值，通过从长期和短期幸存者中分离的显微切割卵巢肿瘤样本的上皮成分的转录组分析确定，并确定其在卵巢癌发病机制中的作用。肿瘤组织切片中ELF 3的免疫组化分析表明，ELF 3仅由上皮性卵巢癌细胞表达。此外，使用从患者中分离的112个高级别卵巢癌样本和癌症基因组图谱（TCGA）数据，我们发现ELF 3表达的下调与生存率降低显著相关。功能研究表明，ELF 3在卵巢癌细胞中的过表达抑制了细胞的增殖和锚定依赖性生长，ELF 3沉默增加了细胞增殖。此外，在卵巢癌细胞中，ELF 3的上调增加了上皮标志物的表达，降低了间充质标志物的表达，并介导了上皮-间充质转化（EMT）信号分子的易位。最后，我们使用动物模型验证了ELF 3的肿瘤抑制作用。总之，ELF 3是卵巢癌的一个有利的预后标志物。ELF 3作为EMT的负调控因子，调控EMT逆转可能成为卵巢癌治疗的一种新的有效模式。
Transcription factors are master switches for various biochemical pathways. However, transcription factors involved in the pathogenesis of ovarian cancer have yet to be explored thoroughly. Therefore, in the present study, we assessed the prognostic value of the transcription factor E74-like factor 3 (ELF3) identified via transcriptome profiling of the epithelial components of microdissected ovarian tumor samples isolated from long- and short-term survivors and determined its roles in ovarian cancer pathogenesis. Immunohistochemical analysis of ELF3 in tumor tissue sections suggested that ELF3 was exclusively expressed by epithelial ovarian cancer cells. Furthermore, using 112 high-grade ovarian cancer samples isolated from patients and The Cancer Genome Atlas (TCGA) data, we found that downregulation of ELF3 expression was markedly associated with reduced survival. Functional studies demonstrated that overexpression of ELF3 in ovarian cancer cells suppressed proliferation and anchorage-dependent growth of the cells and that ELF3 silencing increased cell proliferation. Furthermore, upregulation of ELF3 increased expression of epithelial markers, decreased expression of mesenchymal markers, and mediated translocation of epithelial-mesenchymal transition (EMT) signaling molecules in ovarian cancer cells. Finally, we validated the tumor-inhibitory roles of ELF3 using animal models. In conclusion, ELF3 is a favorable prognostic marker for ovarian cancer. As a negative regulator of EMT, ELF3-modulated reversal of EMT may be a new effective modality in the treatment of ovarian cancer.