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Scripps research scientists illuminate cancer cells' survival strategy
Date:1/26/2012

LA JOLLA, CA -- A team led by scientists at The Scripps Research Institute has discovered key elements of a strategy commonly used by tumor cells to survive when they spread to distant organs. The finding could lead to drugs that could inhibit this metastasis in patients with tumors.

A cell that breaks away from the primary tumor and finds itself in the alien environment of the bloodstream or a new organ, normally is destroyed by a process known as apoptosis. But tumor cells that express high levels of a certain surface protein are protected from apoptosis, greatly enhancing their ability to colonize distant organs. How this protein blocks apoptosis and promotes metastasis has been a mysteryuntil now.

"What we found in this study is that it's not the increased expression of the protein per se that protects a tumor cell, but, rather, the cleavage of this protein by proteolytic enzymes," said Scripps Research Professor James P. Quigley. "This cleavage triggers a signaling cascade in the tumor cell that blocks apoptosis." Quigley is the principal investigator for the study, which was recently published online before print by the journal Oncogene.

"We think that a reasonable strategy for inhibiting metastasis would be to try to prevent the cleavage of this surface protein using antibodies or small-molecule drugs that bind to the cleavage site of the protein," said Elena I. Deryugina, a staff scientist in Quigley's laboratory and corresponding author of the manuscript.

A Protein Linked to Poor Outcomes

The cell-surface protein at the center of this research is known as CUB Domain Containing Protein 1 (CDCP1). In 2003, a postdoctoral fellow in Quigley's laboratory, John D. Hooper, discovered and co-named CDCP1 as a "Subtractive Immunization Metastasis Antigen," also finding that it is highly expressed on the surfaces of metastasis-prone human tumor cells.

Quigley's laboratory and others soon fou
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Contact: Mika Ono
mikaono@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert  

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