Microarray analysis of gene expression during epithelial-mesenchymal transformation.

One of the most fundamental biological processes in development, as well as a primary mechanism for tumor metastasis, is epithelial-mesenchymal transformation (EMT). To gain a greater understanding of this transition, we have obtained a genomic profile of the critical stages before and during this rapid change in morphology in the developing mouse palate. By isolating the medial edge epithelium of each palatal shelf, we were able to obtain pure gene expression data without contamination from surrounding mesenchymal cells. Our results support the important role of the TGF-beta/Smad signal transduction pathway in the stimulation of EMT by means of up-regulation of the EMT-inducing gene, LEF-1. We document changes in gene expression profiles during palatal adherence and subsequent transformation of the medial edge epithelial seam that suggests a high number of LEF-1 target genes promote cellular transformation to mesenchyme. These include genes involved in cell adhesion, polarity, cytoskeletal dynamics, migration, and intracellular signaling. This knowledge of the changes in gene expression levels during palatogenesis should lead to a better understanding of the mechanisms of EMT.

Transforming growth factor-beta signaling during epithelial-mesenchymal transformation: implications for embryogenesis and tumor metastasis.

The molecular mechanisms of epithelial-mesenchymal transformation (EMT) have long been studied to gain a greater understanding of this distinct change in cellular morphology. Early studies of the developing embryo have designated the involvement of Wnt signaling in EMT, through an activated complex of the lymphoid-enhancing factor-1 (LEF-1) transcription factor and the cell adhesion molecule beta-catenin. However, more recent studies have implicated a significant role of the transforming growth factor-beta (TGF-beta) in causing EMT in both development and pathology. The ability of TGF-beta isoforms to signal through a variety of molecules such as Smads, phosphatidylinositol 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK) creates an incredible complexity as to their role in this transition. Here we assess the biochemical signaling pathways of TGF-beta and their potential cross-interaction with traditional Wnt signaling molecules to bring about EMT during embryogenesis and tumor metastasis.