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首页> 外文期刊>Cell death and differentiation >Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression
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Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression

机译：确定控制黑素生成和黑色素瘤进展的ZEB2-MITF-ZEB1转录网络

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Deregulation of signaling pathways that control differentiation, expansion and migration of neural crest-derived melanoblasts during normal development contributes also to melanoma progression and metastasis. Although several epithelial-to-mesenchymal (EMT) transcription factors, such as zinc finger E-box binding protein 1 (ZEB1) and ZEB2, have been implicated in neural crest cell biology, little is known about their role in melanocyte homeostasis and melanoma. Here we show that mice lacking Zeb2 in the melanocyte lineage exhibit a melanoblast migration defect and, unexpectedly, a severe melanocyte differentiation defect. Loss of Zeb2 in the melanocyte lineage results in a downregulation of the Microphthalmia-associated transcription factor (Mitf) and melanocyte differentiation markers concomitant with an upregulation of Zeb1. We identify a transcriptional signaling network in which the EMT transcription factor ZEB2 regulates MITF levels to control melanocyte differentiation. Moreover, our data are also relevant for human melanomagenesis as loss of ZEB2 expression is associated with reduced patient survival.
机译：在正常发育过程中，控制神经c衍生的黑素母细胞分化，扩展和迁移的信号通路的失调也有助于黑色素瘤的进展和转移。尽管几种上皮间质（EMT）转录因子，例如锌指E-box结合蛋白1（ZEB1）和ZEB2，已与神经neural细胞生物学有关，但对其在黑素细胞稳态和黑素瘤中的作用了解甚少。在这里，我们显示在黑素细胞谱系中缺乏Zeb2的小鼠表现出黑素细胞迁移缺陷，出乎意料的是，严重的黑素细胞分化缺陷。黑色素细胞谱系中Zeb2的丢失导致小眼症相关转录因子（Mitf）和黑色素细胞分化标志物的下调与Zeb1的上调。我们确定其中EMT转录因子ZEB2调节MITF水平以控制黑素细胞分化的转录信号网络。此外，我们的数据也与人类黑色素瘤发生有关，因为ZEB2表达的丧失与患者生存率降低有关。

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