What Makes Epithelial Cells Change Their Identity?

During development and during pathological processes in the adult, cells are constantly changing their function. One, well-characterized, cellular transition that occurs during development, as well as during wound healing, tissue fibrosis, and tumor metastasis, is the transition from an epithelial cell to a mesenchymal cell (often a fibroblast). This change in cell type and function is known as epithelial-mesenchymal transition (EMT) and it has been shown that a protein known as FSP1 is important for this transition. However, the proteins that direct the change in the pattern of genes expressed, so that epithelial cells can undergo EMT, have not been completely defined.

In a study appearing in the February issue of the Journal of Clinical Investigation, Eric Neilson and colleagues from Vanderbilt University, Nashville, identify two proteins, CBF-A and KAP-1, as crucial for initiating EMT. CBF-A and KAP-1 were shown, by two independent mechanisms, to bind a regulatory region of DNA in the gene encoding FSP1. This regulatory region of DNA is known as FTS-1 and the binding of proteins to FTS-1 has previously been shown to drive the expression of FSP1. Further analysis by Neilson and colleagues showed that in kidney epithelial cells engineered to express CBF-A a complex composed of CBF-A, KAP-1, and FST-1 formed and that this triggered EMT. This study indicated that the CBF-A/KAP-1/FTS-1 complex is an early regulator of EMT and the authors suggest that it might be the master regulatory complex in this important process.

In an accompanying commentary, Raghu Kalluri and colleagues from Harvard Medical School, Boston, clarify the importance of this study for our understanding of EMT and suggest that the CBF-A/KAP-1/FTS-1 complex might be a good therapeutic target for the treatment of diseases in which EMT features prominently, such as tissue fibrosis.

TITLE: A proximal activator of transcription in epithelial-mesenchymal transition

AUTHOR CONTACT:
Eric G. Neilson
Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

TITLE: Transcriptional regulation of epithelial-mesenchymal transition

AUTHOR CONTACT:
Raghu Kalluri
Harvard Medical School, Boston, Massachusetts, USA.

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JCI table of contents: Feb. 1, 2007

Contact: Karen Honey
Journal of Clinical Investigation