Syndecan-2 regulates cell migration in colon cancer cells through Tiam1-mediated Rac activation.
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.
Choi
Youngsil
Y
Department of Life Sciences, Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, Seoul 120-750, Republic of Korea.
Kim
Hyunjung
H
Chung
Heesung
H
Hwang
Ji-Sun
JS
Shin
Jin-A
JA
Han
Inn-Oc
IO
Oh
Eok-Soo
ES
D002277:Carcinoma / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004789:Enzyme Activation; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D053669:Syndecan-2 / Q000378:metabolism*; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
D020662:Guanine Nucleotide Exchange Factors; C508245:SDC2 protein, human; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human; D053669:Syndecan-2; D051057:Proto-Oncogene Proteins c-akt