Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

By D. Micalizzi, S. Farabaugh, H. Ford. Journal of mammary gland biology and neoplasia, 2010

984 citations recorded by the source corpus.

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer.

View Paper: https://www.semanticscholar.org/paper/0753baabc3b04803c2fd9c7c1bcf258c77f2e799

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Citations in the corpus

• Implications of the Hybrid Epithelial/Mesenchymal Phenotype in Metastasis (2015, background): “…an “all-or-none” process is relatively recent in EMT associated with cancer and fibrosis, but has been generally accepted in wound healing and collective cell migration during embryonic development, especially gastrulation, neural crest migration, and branching morphogenesis (9, 10, 96, 213, 214).”
• EMT and tumor metastasis (2015, background): “More recently, the role of adherent EMT in pathogenesis of fibrosis and metastasis of certain carcinogenic tumors has been described [1-13].”
• Hallmarks of cancer: the next generation. (2011, unknown): “…tumor types and have been shown in experimental models of carcinoma formation to be causally important for programming invasion; some have been found to elicit metastasis when ectopically overexpressed (Micalizzi et al., 2010; Taube et al., 2010; Schmalhofer et al., 2009; Yang and Weinberg, 2008).”