Department of Medical Oncology, Jinling Hospital, Nanjing Medical University, Nanjing, China.
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Gene. 2018 Sep 5;670:7-14. doi: 10.1016/j.gene.2018.05.089. Epub 2018 May 23.
Epithelial-mesenchymal transition (EMT) is a key developmental program in which epithelial cells lose polarity and become mesenchymal cells, and that is often activated during cancer invasion and metastasis. Triple negative breast cancer (TNBC) patients have a relatively aggressive biological behavior with a high risk of distant recurrence and metastasis. Here, we stimulated TNBC cells to undergo EMT, and detected the protein expression profiles of the protein secretion. High-throughput data showed that EMT could promote TNBC cells to secret PAI-1. We found that TNBC-secreted PAI-1 could increase cell growth, migration and invasion, and the expression of EMT markers in the TNBC cell lines and xenograft PAI-1-/- mice model. Using a tissues microarray of 165 TNBC patients and published breast cancer database, we found PAI-1 expression was significantly elevated in the breast cancer tissues, comparing with the normal adjacent tissues and was associated with prognosis of patients with TNBC. Taken together, our results suggests an important role of PAI-1 in the EMT process of TNBC cells and illustrates the great potential of developing PAI-1-targeting therapy for clinical TNBC patients.
上皮-间充质转化（EMT）是一个关键的发育程序，在此过程中上皮细胞失去极性并变成间充质细胞，这一过程通常在癌症侵袭和转移时被激活。三阴性乳腺癌（TNBC）患者具有相对侵袭性的生物学行为，远处复发和转移的风险较高。在这里，我们刺激 TNBC 细胞发生 EMT，并检测了蛋白质分泌的蛋白质表达谱。高通量数据表明，EMT 可促进 TNBC 细胞分泌 PAI-1。我们发现 TNBC 分泌的 PAI-1 可增加 TNBC 细胞系和异种移植 PAI-1-/-小鼠模型中的细胞生长、迁移和侵袭，以及 EMT 标志物的表达。通过对 165 例 TNBC 患者的组织微阵列和已发表的乳腺癌数据库进行研究，我们发现 PAI-1 的表达在乳腺癌组织中显著升高，与正常相邻组织相比，并与 TNBC 患者的预后相关。综上所述，我们的研究结果表明 PAI-1 在 TNBC 细胞的 EMT 过程中起着重要作用，并说明了针对 PAI-1 的靶向治疗在临床上对 TNBC 患者具有巨大的潜力。
