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LSUHSC research finds trigger for breast cancer spread
Date:1/3/2012

amino acids for recycling. Such proteins are marked for degradation by flagging them with a small protein called Ubiquitin, which is then recognized by the Proteasome. Alterations in the genetic program that controls the Ubiquitin/Proteasome system have been known for some time to cause cell transformation and cancer. More recently, Dr. Desai and her colleagues have demonstrated that, unlike normal cells, transformed cancer cells produce increased amounts of a related control system that marks proteins with another small protein called ISG15.

Previous research reports that the amount of ISG15 is increased in high-grade compared with low-grade cancers. The ISG15 system is normally activated by interferon and is part of an ancient cellular immune response designed to counter bacterial and viral infection. By a still unidentified mechanism, cancer cell transformation activates the ISG15 pathway. Dr. Desai and colleagues have previously reported that activation of the ISG15 system interferes with function of the Ubiquitin/Proteasome pathway. In their latest work, Dr. Desai and colleagues show that several key proteins that regulate cell movement, invasion, and metastasis are blocked from Proteasome degradation by the ISG15 system and that genetic manipulation to inhibit this pathway reverses cancer cell transformation, suggesting an approach to blocking cancer progression.

Arthur Haas, PhD, the Roland Coulson Professor and Chairman of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, discovered the ISG15 pathway and co-discovered the Ubiquitin/Proteasome system that was awarded the 2004 Nobel Prize in Chemistry. "These results provide a functional link between the Ubiquitin and ISG15 pathways that reveals how small cell alterations can yield large overall consequences for cell transformation."

The research team also included Arthur Haas, PhD, and Dr. Desai's lab members Ryan Reed, Surendran Sankar, PhD, and Julian Bur
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Contact: Leslie Capo
lcapo@lsuhsc.edu
504-568-4806
Louisiana State University Health Sciences Center
Source:Eurekalert

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