New Orleans, LA Research led by David Worthylake, PhD, Assistant Professor of Biochemistry and Molecular Biology at LSU Health Sciences Center New Orleans, may help lay the groundwork for the development of a compound to prevent the spread of cancer. The research will be published in the May 29, 2009 issue of the Journal of Biological Chemistry.
During the transition from a localized tumor to metastatic disease, cancer cells acquire the ability to detach from their neighboring cells and move to and invade tissue at distant points in the body.
"Because tumor metastasis leads to a poor prognosis and tremendously complicates treatment, it is of utmost importance that we understand, at a molecular level, the processes that regulate cell adhesion, migration and invasion," notes Dr. Worthylake.
He and his colleagues studied a protein in cells that is involved in regulating cell structure, cell-to-cell contact, and cell movement. When too much of this protein, called IQGAP1, is produced, it can weaken cell-to-cell contacts and promote cell migration and invasion processes that occur during tumor metastasis.
The research team focused on the area of IQGAP1 that interacts with two smaller proteins Cdc42 and Rac which, when activated, contribute to cell destabilization, cell movement, and invasion. This region on IQGAP1 is related to proteins that accelerate deactivation of another small protein similar to Cdc42 and Rac. However, IQGAP1 does not deactivate Cdc42 and Rac in fact, IQGAP1 prolongs their activated states. The researchers determined the atomic structure of this region of IQGAP1 and furthermore, built a model of their IQGAP1 structure bound to the previously determined structure of Cdc42 in order to understand why IQGAP1 does not deactivate Cdc42. The model provides detailed information about the (likely) specific contacts made between IQGAP1 and Cdc42. The model also shows that IQGAP1 is missing a key compon
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Louisiana State University Health Sciences Center