Epithelial–mesenchymal transition (EMT) programs play essential functions in normal morphogenesis and organogenesis, including that occurring during mammary gland development and glandular regeneration. Historically, EMT programs were believed to reflect a loss of epithelial gene expression signatures and morphologies that give way to those associated with mesenchymal cells and their enhanced migratory and invasive behaviors. However, accumulating evidence now paints EMT programs as representing a spectrum of phenotypic behaviors that also serve to enhance cell survival, immune tolerance, and perhaps even metastatic dormancy. Equally important, the activation of EMT programs in transformed mammary epithelial cells not only enhances their acquisition of invasive and metastatic behaviors, but also expands their generation of chemoresistant breast cancer stem cells (BCSC). Importantly, the net effect of these events results in the appearance of recurrent metastatic lesions that remain refractory to the armamentarium of chemotherapies and targeted therapeutic agents deployed against advanced stage breast cancers. Here we review the molecular and cellular mechanisms that contribute to the pathophysiology of EMT programs in human breast cancers and how these events impact their “stemness” and acquisition of chemoresistant phenotypes.

中文翻译：

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上皮-间质转化计划和癌症干细胞表型：乳腺癌治疗耐药的介质

上皮-间质转化 (EMT) 程序在正常形态发生和器官发生中发挥重要作用，包括在乳腺发育和腺体再生过程中发生的那些。从历史上看，EMT 程序被认为反映了上皮基因表达特征和形态的丧失，这些特征和形态让位于与间充质细胞及其增强的迁移和侵入行为相关的那些。然而，越来越多的证据现在将 EMT 程序描绘为代表一系列表型行为，这些行为也有助于提高细胞存活率、免疫耐受性，甚至可能是转移性休眠。同样重要的是，在转化的乳腺上皮细胞中激活 EMT 程序不仅增强了它们对侵袭和转移行为的习得，但也扩大了他们的耐化学性乳腺癌干细胞 (BCSC) 的产生。重要的是，这些事件的净效应导致出现复发性转移性病变，这些病变对于晚期乳腺癌的化疗和靶向治疗药物仍然难以治愈。在这里，我们回顾了有助于人类乳腺癌 EMT 程序病理生理学的分子和细胞机制，以及这些事件如何影响它们的“干性”和化学抗性表型的获得。