| Metastasis is the main cause of cancer related mortality, largely owing to its refractory response to therapy. In spite of over a century of research, many of the mechanisms underlying metastasis are unknown, especially that of escape from the primary tumor. One potential hypothesis is the epithelial- mesenchymal transition (EMT), in which primary tumor epithelial cells transform into motile mesenchymal cells that have the capacity to intravasate, circulate, and establish a secondary tumor. The last step is mediated by the reverse process, mesenchymal-epithelial transition (MET), in which the cells revert to an epithelial morphology.;The role of the EMT in metastasis is a longstanding source of controversy, largely due to an inability to monitor transient and reversible EMT phenotypes in vivo. We established an EMT lineage tracing system to illuminate this process, using a mesenchymal-specific Cre-mediated fluorescent marker switch system in spontaneous breast-to-lung metastasis models. We confirmed that within a predominantly epithelial primary tumor, a small portion of tumor cells undergo EMT. Strikingly, lung metastases were mainly comprised of non-EMT tumor cells maintaining their epithelial phenotype. Inhibiting EMT by overexpressing miR-200 did not impact lung metastasis development. As a result, we conclude that EMT is not required for metastasis. |
