Expression of the 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-down 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.
|Number of pages||5|
|Journal||Biochemical and Biophysical Research Communications|
|State||Published - 1 Jan 2010|
Bibliographical noteFunding Information:
This study was supported by a grant of the Research at National R&D Program for Cancer Control, Ministry of Health & Welfare , Republic of Korea ( 0420070-1 to E.S.O.) and Grant No. R15-2006-020 from the NCRC program of the MOST and the KOSEF through the Center for Cell Signaling & Drug Discovery Ewha Womans University .
- Cell migration
- Colon cancer
- Signal transduction