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

helial cells and IIIc, which is expressed in mesenchymal cells. The protein that is made from the IIIb form interacts with factors outside the cell that promote the epithelial cell behavior, that is to remain stationary. When the IIIc form is aberrantly produced in cancer cells derived from epithelial cells, the resulting FGFR2 protein type no longer promotes the epithelial cell identity, and switches to the mesenchymal cell type, which has the ability to detach from its primary site, invade local tissue and migrate, or metastasize to distant sites of the body.

"If we can find a way to maintain expression of ESRP1 and 2 in epithelial cells, then it might be possible to prevent metastasis or control fibrosis," notes corresponding author Russ P. Carstens, MD, Assistant Professor of Medicine. "ESRP1 and ESRP2 are necessary for splicing FGFR2 mRNA in the epithelial cell manner. This is one of few known splicing factors that operate in a clear cut cell-type-specific manner. Epithelial cells, which make up the lining of organs, are the only cells that produce ESRP1 and ESRP2."

To discover ESRP1 and ESRP2, the team used a high-throughput genetic screen for rare proteins developed by collaborator and co-author John B. Hogenesch, PhD, Associate Professor of Pharmacology, an innovator in the use of these types of screens. In addition, Claude Warzecha, a graduate student in the Carstens lab, played a key role in the completion of the screen.

The screen consists of about 15,000 different cDNAs (DNA that has been synthesized from messenger RNAs) that each express a different gene and are arrayed on plates so that each well of the plate expresses only one individual gene product. The Carstens lab developed a splicing "reporter" that makes cells express a firefly luciferase gene and "glow" when it is spliced in the epithelial cell pattern. Cells with this reporter were individually placed over wells containing each cDNA and cells that "glowed, indi
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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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