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Mitotic Regulator Gets Moving

The cyclin-dependent kinase Cdc2 is usually thought of as a promoter of mitosis. Manes et al. describe a possible new role for Cdc2 in regulating cell migration. Expression of the αvβ3 integrin is associated with migratory and invasive behaviors of some cancer cells. Therefore, Manes et al. isolated genes that showed increased expression in a prostate cancer cell line overexpressing αvβ3 integrin and identified Cdc2. Ectopic expression of Cdc2 increased migration in cell lines. Conversely, inhibition of Cdc2 activity by expression of a dominant negative or with pharmacological inhibitors reduced migration of cultured cells. In HeLa cells, Cdc2 was located at lamellipodia. The authors propose caldesmon as a potential target of Cdc2. Caldesmon is an actin-binding protein that associates with membrane ruffles and appears to be a substrate for Cdc2. Prostate cancers often show increased expression of αvβ3 integrin, and increased expression of Cdc2 in prostate cancer correlates with more aggressive cancers. Thus, the authors note that key actions of Cdc2 in this instance may occur through promotion of migration and invasion rather than through the more expected role in promotion of cell proliferation. T. Manes, D.-Q. Zheng, S. Tognin, A. S. Woodard, P. C. Marchisio, L. R. Languino, αvβ3 integrin expression up-regulates Cdc2, which modulates cell migration. J. Cell Biol. 161, 817-826 (2003). [Abstract] [Full Text]