Context Dependency of Epithelial-to-Mesenchymal Transition for Metastasis

Abstract

Summary: Epithelial-to-mesenchymal transition (EMT) has been proposed to be important for metastatic dissemination. However, recent studies have challenged the requirement of EMT for metastasis. Here, we assessed in different models of primary skin squamous cell carcinomas (SCCs) whether EMT is associated with metastasis. The incidence of metastasis was much higher in SCCs presenting EMT compared to SCCs without EMT, supporting the notion that a certain degree of EMT is required to initiate the metastatic cascade in primary skin SCCs. Most circulating tumor cells presented EMT, whereas most lung metastasis did not present EMT, showing that mesenchymal-to-epithelial transition is important for metastatic colonization. In contrast, immunodeficient mice transplanted with SCCs, whether displaying EMT or not, presented metastasis. Altogether, our data demonstrate that the association of EMT and metastasis is model dependent, and metastasis of primary skin SCCs is associated with EMT. : The role of epithelial-to-mesenchymal transition (EMT) during metastasis remains controversial. Revenco et al. show that in models of primary skin tumors, only EMT tumors are associated with metastasis. In contrast, EMT is not required to induce metastasis following the subcutaneous transplantation of tumor cells, demonstrating the context dependency of EMT for metastasis. Keywords: EMT, MET, metastasis, cancer, primary tumor, circulating tumor cells, tumor transplantation, niche, cancer stem cells