CHAPEL HILL -- Scientists from the University of North Carolina atChapel Hill School of Medicine and the UNC Lineberger ComprehensiveCancer Center have identified a protein that may inhibit cellularmovement, or migration.
The protein, CIB1, or calcium and integrin-binding protein 1, wasoriginally discovered at UNC in 1997 as a blood platelet protein thatmay play a role in clotting.
Cell migration belongs to the most rudimentary of cellular functionsthat allow processes such as fetal development, new blood vesselformation and wound healing to occur in humans. Increased tumor cellmigration also is one of the hallmarks of highly aggressive, rapidlyspreading cancer tumors.
The study appears in the August issue of The Journal of Cell Biology.
The study indicates that CIB1 inhibits cell migration by binding to andactivating a protein called PAK1, or p21-activated kinase, in cancercells. When CIB1 activates PAK1, this kinase then inhibits cellmigration by adding a phosphate group to a host of other proteins inthe cell.
Thus, the study suggests that CIB1 may be a likely target for new drugdevelopment aimed at decreasing tumor metastasis, or spread, throughoutthe body.
"I was ecstatic to see these results and to discover that it alsoregulates the fundamental process of cell migration," said Dr. TinaLeisner, associate professor of pharmacology at UNC and the study'slead author."CIB1 plays a prominent role in the activation of PAK1 and potentiallymay be another important player in the regulation of this kinase," sheadded.
The other activators of PAK1 include relatives of the notorious Rasfamily of tumor promoters, the GTPases Rac and Cdc42. CIB1 activationof PAK1, however, is different from these GTPases.
"CIB1 activates PAK1 before Rac and Cdc42," said Dr. Leslie V. Parise,UNC professor of pharmacology, member of UNC Lineberger and the study'ssenior author.
"The time course of PAK1 activation never synched up with the timecourse of Rac and Cdc42 activation; now we know why � it was probablyCIB1 that was activating PAK1 and not the Ras relatives."
In illustrating the role that CIB1 plays in cell migration and PAK1activation, the authors used a new method known as RNAi or RNAinterference to knock down or reduce CIB1 expression in various celllines. Cells with le/p>
Materials provided by University of North Carolina School of Medicine. Note: Content may be edited for style and length.
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