Context Dependency of Epithelial-to-Mesenchymal Transition for Metastasis

Cell Rep. 2019 Nov 5;29(6):1458-1468.e3. doi: 10.1016/j.celrep.2019.09.081.


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.

Keywords: EMT; MET; cancer; cancer stem cells; circulating tumor cells; metastasis; niche; primary tumor; tumor transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary*
  • Epithelial Cell Adhesion Molecule / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • Incidence
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Neoplasm Transplantation
  • Neoplastic Cells, Circulating / metabolism*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Transplantation, Homologous


  • Epithelial Cell Adhesion Molecule