Epithelial–Mesenchymal Transition in Development and Cancer

Abstract

The epithelial–mesenchymal transition (EMT) is a critical developmental process from the earliest events of embryogenesis to later morphogenesis and organ formation. EMT contributes to the complex architecture of the embryo by permitting the progression of embryogenesis from a simple single-cell layer epithelium to a complex three-dimensional organism composed of both epithelial and mesenchymal cells. However, in most tissues EMT is a developmentally restricted process and fully differentiated epithelia typically maintain their epithelial phenotype. Recently, elements of EMT, specifically the loss of epithelial markers and the gain of mesenchymal markers, have been observed in pathological states, including epithelial cancers. Analysis of the molecular mechanisms of this oncogenic epithelial plasticity have implicated the inappropriate expression and activation of developmental EMT programs, suggesting that cancer cells may reinstitute properties of developmental EMT including enhanced migration and invasion. Thus, in the context of cancer, an EMT-like process may permit dissemination of tumor cells from the primary tumor into the surrounding stroma, setting the stage for metastatic spread. Consistent with this hypothesis, activation of these developmental EMT programs in human cancer correlates with advanced disease and poor prognosis. This review will focus on the current knowledge regarding developmental EMT pathways that have been implicated in cancer progression.

Keywords:

• cancer
• development
• epithelial–mesenchymal transition
• metastasis
• Six1
• Snail/Slug
• TGF-β
• Twist
• Wnt

Financial & competing interests disclosure

Heide L Ford was funded by grants from the National Cancer Institute (2RO1-CA095277), The American Cancer Society (#RSG-07–183–101-DDC), The Susan G Komen Foundation (BCTR0707562), and the Cancer League of Colorado. Douglas S Micalizzi was funded by a predoctoral fellowship from the Department of Defense Breast Cancer Research Program (W81XWH-06-01-0757). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Heide L Ford was funded by grants from the National Cancer Institute (2RO1-CA095277), The American Cancer Society (#RSG-07–183–101-DDC), The Susan G Komen Foundation (BCTR0707562), and the Cancer League of Colorado. Douglas S Micalizzi was funded by a predoctoral fellowship from the Department of Defense Breast Cancer Research Program (W81XWH-06-01-0757). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.