The aim of the present study was to evaluate the effect of ETS homologous factor (EHF) in malignant breast cancer cells. The overexpression and knockdown of the EHF gene in human and mouse breast cancer cells were performed, and the TCGA dataset and Q-omics were analyzed. We found that the tumor suppressor NDRG2 is correlated with EHF gene expression in triple-negative breast cancer cells, that EHF overexpression results in reduced cell proliferation and that apoptosis is promoted by the chemotherapeutic reagent treatment of EHF-overexpressing cells. By EHF overexpression, senescence-associated β-galactosidase activity and p21WAF1/CIP1expression were increased, suggesting that EHF may induce cellular senescence. In addition, the overexpression of EHF reduced the migratory ability and inhibited epithelial–mesenchymal transition (EMT). Furthermore, EHF inhibited the phosphorylation of STAT3. The overexpression of EHF also reduced the tumor size, and lung metastasis in vivo. At the tumor site, β-galactosidase activity was increased by EHF. Finally, the Kaplan–Meier-plotter analysis showed that TNBC patients with a high expression of EHF had a longer relapse-free survival rate. Our findings demonstrated that EHF inhibits breast tumor progression by inducing senescence and regulating EMT in TNBC cells.
本研究旨在评估ETS同源因子（EHF）在恶性乳腺癌细胞中的作用。我们在人源及小鼠乳腺癌细胞中进行了EHF基因的过表达与敲低操作，并分析了TCGA数据集及Q-omics数据。研究发现，在三阴性乳腺癌细胞中，抑癌基因NDRG2与EHF基因表达呈相关性；EHF过表达可降低细胞增殖能力，且经化疗药物处理的EHF过表达细胞其凋亡过程被促进。通过EHF过表达，衰老相关β-半乳糖苷酶活性及p21WAF1/CIP1表达均有所增加，提示EHF可能诱导细胞衰老。此外，EHF过表达降低了细胞迁移能力并抑制上皮-间质转化（EMT）。EHF还能抑制STAT3的磷酸化。在体内实验中，EHF过表达同样减少了肿瘤体积并抑制肺转移。在肿瘤部位，EHF提高了β-半乳糖苷酶活性。最后，Kaplan-Meier生存分析显示，EHF高表达的三阴性乳腺癌患者具有更长的无复发生存期。我们的研究结果表明，EHF通过诱导衰老并调控三阴性乳腺癌细胞的EMT过程抑制乳腺肿瘤进展。
肿瘤(癌症)患者之家