Cell reports：单基因可将健康细胞变为移动的癌症工厂

9月16日讯 /生物谷BIOON/ --单个干细胞具有形成多细胞个体的潜能。许多肿瘤中都包含一些干细胞样的异常细胞，它们就像是小型的工厂，不仅能够快速的进行自我复制，还会发生变异以更好地应对环境的挑战。更加糟糕的是，这些干细胞样的肿瘤细胞还会扩散到其他组织，引起肿瘤的转移。来自美国萨克研究所的研究人员在国际学术期刊cell reports上发表了一项最新研究进展，他们向人们展示了一个叫做Sox10的关键基因如何将细胞变成了危险的"癌症工厂"。对于Sox10的新理解或将帮助科学家们找到治疗抗药肿瘤的更有效方法。在这项新研究中，研究人员首先筛选了在正常乳腺干细胞和乳腺癌组织中都存在高表达的基因，其中一个便是Sox10，它参与了调控细胞分化成为成熟组织的过程。研究人员发现具有产生多种不同类型细胞能力的乳腺干细胞具有很高水平的Sox10表达，如果将这些细胞中的Sox10移除，这些细胞将失去这种多能性。研究人员还发现在适当条件下，高水平的Sox10蛋白会引起另外一种让人意想不到的特性：乳腺细胞会发生间充质转化并侵入到周围区域。研究人员指出："我们目前已经掌握了Sox10与肿瘤生长发展，可塑性和传播潜能相关的功能性证据，Sox10可能是导致乳腺癌具备致命特性的关键驱动因素。"该研究组计划进一步研究消除Sox10的功能是否可以治疗乳腺癌并阻断其转移，他们希望接下来对这一重要基因的研究可以发现其他信号途径帮助阻断Sox10诱导的肿瘤进展。（生物谷）本文系生物谷原创编译整理。欢迎转载！转载请注明来源并附原文链接。更多资讯请下载。Sox10 Regulates Stem/Progenitor and Mesenchymal Cell States in Mammary Epithelial CellsChristopher Dravis, Benjamin T. Spike, J. Chuck Harrell, Claire Johns, Christy L. Trejo, E. Michelle Southard-Smith, Charles M. Perou, Geoffrey M. WahlTo discover mechanisms that mediate plasticity in mammary cells, we characterized signaling networks that are present in the mammary stem cells responsible for fetal and adult mammary development. These analyses identified a signaling axis between FGF signaling and the transcription factor Sox10. Here, we show that Sox10 is specifically expressed in mammary cells exhibiting the highest levels of stem/progenitor activity. This includes fetal and adult mammary cells in vivo and mammary organoids in vitro. Sox10 is functionally relevant, as its deletion reduces stem/progenitor competence whereas its overexpression increases stem/progenitor activity. Intriguingly, we also show that Sox10 overexpression causes mammary cells to undergo a mesenchymal transition. Consistent with these findings, Sox10 is preferentially expressed in stem- and mesenchymal-like breast cancers. These results demonstrate a signaling mechanism through which stem and mesenchymal states are acquired in mammary cells and suggest therapeutic avenues in breast cancers for which targeted therapies are currently unavailable.

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