Expression of rile cell surface adhesion receptor syndecan-2 is known to be involved in the regulation of cancer cell migration However, the molecular mechanism of syndecan-2-mediated cell migration remains unknown Here we report that Rac contributes to the regulation of syndecan-2-mediated cancer-cell migration. Overexpression of syndecan-2 enhanced migration and Invasion Of human Colon adenocarcinoma cells Caco-2 and HCT116 cells In parallel with the increased cell migration/invasion, syndecan-2 overexpression enhanced Rac activity. while dominant negative Rac (RacN17) diminished syndecan-2-mediated increased cancer cell migration In addition syndecan-2 expression Increased membrane localization of Tiam1 and syndecan-2-mediated cell migration/invasion of Caco-2 cells was diminished when Tiam1 levels were knocked-clown with small inhibitory RNAs Furthermore, oligomerization-defective syndecan-2 mutants failed to increase membrane localization of Tiam1. activation of Rac and subsequent cell migration of both Caco-2 and HCT116 cells Taken together, these results suggest that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in colon cancer cells (C) 2009 Elsevier Inc All rights reserved.