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UNC scientists discover new role for protein as fundamental inhibitor of cell movement

Scientists from the University of North Carolina at Chapel Hill School of Medicine and the UNC Lineberger Comprehensive Cancer Center have identified a protein that may inhibit cellular movement, or migration.

The protein, CIB1, or calcium and integrin-binding protein 1, was originally discovered at UNC in 1997 as a blood platelet protein that may play a role in clotting.

Cell migration belongs to the most rudimentary of cellular functions that allow processes such as fetal development, new blood vessel formation and wound healing to occur in humans. Increased tumor cell migration also is one of the hallmarks of highly aggressive, rapidly spreading 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 and activating a protein called PAK1, or p21-activated kinase, in cancer cells. When CIB1 activates PAK1, this kinase then inhibits cell migration by adding a phosphate group to a host of other proteins in the cell.

Thus, the study suggests that CIB1 may be a likely target for new drug development aimed at decreasing tumor metastasis, or spread, throughout the body.

"I was ecstatic to see these results and to discover that it also regulates the fundamental process of cell migration," said Dr. Tina Leisner, associate professor of pharmacology at UNC and the study's lead author. "CIB1 plays a prominent role in the activation of PAK1 and potentially may be another important player in the regulation of this kinase," she added.

The other activators of PAK1 include relatives of the notorious Ras family of tumor promoters, the GTPases Rac and Cdc42. CIB1 activation of 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's senior author.

"The time course of PAK1 activation nev
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Source:University of North Carolina School of Medicine


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