Li Yanlin, Wu Tiantian, Peng Ziluo, Tian Xianyan, Dai Qian, Chen Miao, Zhu Jun, Xia Song, Sun Aiqin, Yang Wannian, Lin Qiong
School of Medicine, Jiangsu University Zhenjiang, Jiangsu, China.
Department of Clinical Laboratory, The First Affiliated Hospital of Anhui Medical University Hefei, Anhui, China.
Am J Cancer Res. 2022 Nov 15;12(11):5074-5084. eCollection 2022.
E26 transcription factor-1 (ETS1) is involved in extracellular matrix remodeling, migratory infiltration and angiogenesis in tumors and known to play an important role in tumor progression. However, the mechanism by which ETS1 promotes tumor progression remains elusive. In this report, we show that ETS1 is highly expressed in breast tumor tissues and specifically associated with the tumor metastasis and poor survival in triple negative breast cancer (TNBC) tumors, upon analysis by immunohistochemical (IHC) staining of tumor samples from 240 breast cancer cases. Depletion of ETS1 in TNBC cells by shETS1 significantly inhibited the cell proliferation and migration. Mechanistically, knockdown of ETS1 in TNBC cells dramatically reduced expression of YAP and the YAP target genes, and overexpression of YAP in the ETS1 knockdown cells restored the cell proliferation and migration. These data indicate that YAP is a downstream effector mediating the ETS1-promoted TNBC cell proliferation and migration. Taken together, our results suggest that ETS1 promotes TNBC progression through the YAP signaling.
E26转录因子-1(ETS1)参与肿瘤细胞外基质重塑、迁移浸润和血管生成,已知其在肿瘤进展中起重要作用。然而,ETS1促进肿瘤进展的机制仍不清楚。在本报告中,我们通过对240例乳腺癌病例的肿瘤样本进行免疫组织化学(IHC)染色分析发现,ETS1在乳腺肿瘤组织中高表达,且与三阴性乳腺癌(TNBC)的肿瘤转移及不良预后密切相关。通过shETS1敲低TNBC细胞中的ETS1可显著抑制细胞增殖和迁移。机制上,敲低TNBC细胞中的ETS1可显著降低YAP及其靶基因的表达,而在ETS1敲低的细胞中过表达YAP可恢复细胞增殖和迁移。这些数据表明YAP是介导ETS1促进TNBC细胞增殖和迁移的下游效应分子。综上所述,我们的结果表明ETS1通过YAP信号通路促进TNBC进展。