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Master molecular switch may prevent the spread of cancer cells to distant sites in the body
Date:3/16/2009

PHILADELPHIA Researchers at the University of Pennsylvania School of Medicine have identified a master switch that might prevent cancer cells from metastasizing from a primary tumor to other organs. The switch is a protein that, when in the "on" position, maintains the normal character of cells that line the surface of organs and body cavities. These epithelial cells are the type of cell from which most solid tumors arise. However, when the switch is turned "off" or absent, epithelial cells acquire characteristics of another cell type, called mesenchymal cells, and gain the ability to migrate and move away from the primary tumor. The researchers report their findings in this month's issue of Molecular Cell.

Understanding how this switch works may one day lead to a drug that controls cancer cell metastasis and tissue fibrosis.

This change in cell motility is called the epithelial to mesenchymal transition, or EMT, and is an important process during the development of embryos. But when the transition is aberrantly reactivated in adults it can have dire physiological consequences, leading to cancer metastasis as well as other disease processes such as tissue fibrosis. Fibrotic tissue is a hallmark of organ failure, as in liver cirrhosis or kidney failure.

The master-switch is called the Epithelial Splicing Regulatory Protein, and comes in two closely related versions, ESRP1 and ESRP2. These proteins are able to change how RNAs that are produced from genes are spliced together. This is achieved by splicing different exons -- the sequence of DNA that codes information for protein synthesis -- together in different ways so that there can be more than one messenger RNA (mRNA) produced from the same gene. These mRNAs then go on to make different proteins.

The mRNA for Fibroblast Growth Factor Receptor 2 (FGFR2) is the focus of the Molecular Cell study. FGFR2 mRNA has two forms, one called IIIb, which is expressed in epit
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert  

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