Sdc1 negatively modulates carcinoma cell motility and invasion.
During cancer progression, tumor cells eventually invade the surrounding collagen-rich extracellular matrix. Here we show that squamous cell carcinoma cells strongly adhere to Type I collagen substrates but display limited motility and invasion on collagen barriers. Further analysis revealed that in addition to the alpha2beta1 integrin, a second collagen receptor was identified as Syndecan-1 (Sdc1), a cell surface heparan sulfate proteoglycan. We demonstrate that siRNA-mediated depletion of Sdc1 reduced adhesion efficiency to collagen I, whereas knockdown of Sdc4 was without effect. Importantly, silencing Sdc1 expression caused reduced focal adhesion plaque formation and enhanced cell spreading and motility on collagen I substrates, but did not alter cell motility on other ECM substrates. Sdc1 depletion ablated adhesion-induced RhoA activation. In contrast, Rac1 was strongly activated following Sdc1 knockdown, suggesting that Sdc1 may mediate the link between integrin-induced actin remodeling and motility. Taken together, these data substantiate the existence of a co-adhesion receptor system in tumor cells, whereby Sdc1 functions as a key regulator of cell motility and cell invasion by modulating RhoA and Rac activity. Downregulation of Sdc1 expression during carcinoma progression may represent a mechanism by which tumor cells become more invasive and metastatic.
Ishikawa
Tohru
T
Department of Cell and Tissue Biology, University of California San Francisco, 521 Parnassus Avenue, Room C-640, San Francisco, CA 94143-0640, USA.
Kramer
Randall H
RH
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D053668:Syndecan-1 / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D024042:Collagen Type I; D038982:Integrin alpha2beta1; D034741:RNA, Small Interfering; D053668:Syndecan-1; D020741:rho GTP-Binding Proteins