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

Abstract

Summary: 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. : Bornes et al. use a combination of fsp1-based lineage-tracing and E-cadherin-based real-time EMT-state reporter. They demonstrate that the majority of disseminating mesenchymal cells in breast tumors are not labeled by the fsp1-mediated lineage-tracing mark but do have metastatic potential. These findings uphold the role of EMT in metastasis. Keywords: epithelial-to-mesenchymal transition, EMT, metastasis, cancer, plasticity, epithelia, mesenchymal, dissemination, E-cadherin, fsp1