Fsp1-Mediated Lineage Tracing Fails to Detect the Majority of Disseminating Cells Undergoing EMT

Fsp1-Mediated Lineage Tracing Fails to Detect the Majority of Disseminating Cells Undergoing EMT
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DOI:
10.1016/j.celrep.2019.10.107
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发表时间:
2019-11-26
期刊:
影响因子:
8.8
通讯作者:
van Rheenen, Jacco
van Rheenen, Jacco
中科院分区:
生物学1区
文献类型:
--
作者:
Bornes, Laura;van Scheppingen, Roan Hugo;van Rheenen, Jacco

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上皮-间质转化(Epithelial-to-mesenchymal transition, EMT)一直被认为是肿瘤转移的关键。最近的一项研究挑战了这一观点,证明转移是由肿瘤细胞播下的,而这些肿瘤细胞没有被EMT谱系追踪报告基因(基于间充质标记物fsp1的表达)标记出来。然而,这项研究的结果及其解释仍存在争议。在这里,我们将谱系追踪报告因子与实时EMT状态报告因子结合起来,并表明基于fsp1的EMT谱系追踪报告因子并不能标记所有具有转移潜力的播散间充质细胞。我们的研究结果表明,fsp1介导的谱系追踪并不能得出关于EMT对转移的要求的任何结论。相反,我们的数据与以前的报告完全一致,即EMT不是二元现象,而是细胞状态的频谱。
Epithelial-to-mesenchymal transition (EMT) has long been thought to be crucial for metastasis. Recently a study challenged this idea by demonstrating that metastases were seeded by tumor cells that were not marked by an EMT lineage-tracing reporter on the basis of the expression of the mesenchymal marker fsp1. However, the results of this study and their interpretation are under debate. Here, we combine the lineage-tracing reporter with our real-time EMT-state reporter and show that the fsp1-based EMT lineage-tracing reporter does not mark all disseminating mesenchymal cells with metastatic potential. Our findings demonstrate that fsp1-mediated lineage tracing does not allow any conclusions about the requirement of EMT for metastasis. Instead our data are fully consistent with previous reports that EMT is not a binary phenomenon but rather a spectrum of cellular states.