TGF-β and epithelial-to-mesenchymal transitions

Abstract

Remarkable phenotype plasticity of epithelial cells underlies morphogenesis, epithelial repair and tumor invasiveness. Detailed understanding of the contextual cues and molecular mediators that control epithelial plasticity will be required in order to develop viable therapeutic approaches targeting epithelial-to-mesenchymal transition (EMT), an advanced manifestation of epithelial plasticity. Members of the transforming growth factor (TGF-b) family of growth factors can initiate and maintain EMT in a variety of biological systems and pathophysiological context by activating major signaling pathways and transcriptional regulators integrated in extensive signaling networks. Here we will review the distinct physiological contexts of EMT and the underlying molecular signaling networks controlled by TGF-b.

Molecular signatures of metaplastic carcinoma of the breast by large-scale transcriptional profiling: identification of genes potentially related to epithelial–mesenchymal transition

“…Although SNAI1 (Snail) and SNAI2 (Slug), which encode zinc-finger proteins crucial in the development of EMT, were identified as MCB-overexpressed genes on SAM analysis at an FDR of 0.05 (data not shown), some genes that are known to be activated during EMT (Zavadil and Bottinger, 2005) were absent in this genome-wide screen. It is possible that some of the molecular participants in EMT could appear only transiently in certain stages during the process of EMT, especially in the context of primary tumors when EMT takes a long time (Thiery, 2002;Zavadil and Bottinger, 2005).…”

“…It is possible that some of the molecular participants in EMT could appear only transiently in certain stages during the process of EMT, especially in the context of primary tumors when EMT takes a long time (Thiery, 2002;Zavadil and Bottinger, 2005). Alternatively, there might be potential differences in these molecular participants not only between embryonic development and cancer progression of different types, but also between in vitro and in vivo observations.…”

“…Epithelial-mesenchymal transition (EMT) is the process of disaggregating structured polarized epithelial units into single-motile fibroblastoid cells to enable cell movement and morphogenesis, which was originally discovered from studies of embryonic development (Zavadil and Bottinger, 2005). The process of EMT gained wide recognition as a potential mechanism for the progression of malignancy, and was attributed to the loosening of epithelial characteristics and the acquisition of migratory and highly matrix invasive phenotypes (Thiery, 2002).…”

“…The process of EMT gained wide recognition as a potential mechanism for the progression of malignancy, and was attributed to the loosening of epithelial characteristics and the acquisition of migratory and highly matrix invasive phenotypes (Thiery, 2002). EMT is characterized by loss of proteins associated with the polarized epithelial phenotype (for example, E-cadherin and cytokeratin) and de novo synthesis of proteins associated with mesenchymal and migratory morphology of transitioning cells (for example, vimentin) (Zavadil and Bottinger, 2005). Classically, MCB is composed of carcinomatous and sarcomatous components.…”

Canonical WNT signalling determines lineage specificity in Wilms tumour

“…Other categories characterizing mesenchymal lineages included genes for transcription factors involved in early mesodermal lineages, chondrogenesis, osteogenesis, hemangiogenesis, adipogenesis and stromagenesis (Table 2a). Another major pathway involved in cluster A was TGF-b (transforming growth factor-b) signalling (TGFB2, FST, BMP1, BMP2, BMP3), which is known to contribute to mesenchymal phenotypes and chondrogenesis (Wang et al, 2005;Zavadil and Bottinger, 2005).…”