Syntenin is overexpressed and promotes cell migration in metastatic human breast and gastric cancer cell lines.
Two human breast cancer cell lines of differing invasive and metastatic potential, MDA-MB-435 and MCF7, were examined using subtractive suppression hybridization in a search for any genes associated with metastasis. Of the 17 cDNAs identified as being differentially expressed genes, it was determined that syntenin was overexpressed in metastatic MDA-MB-435 cells. Expression analysis showed that the expression level of syntenin was well correlated with invasive and metastatic potential in various human breast and gastric cancer cell lines. Moreover, gastric tumor tissues exhibited a much higher syntenin mRNA expression than their normal counterparts. Syntenin-transfected MCF7 cells migrated more actively, and showed an increased invasion rate relative to vector-transfectants or parental MCF7 in vitro, without evidencing any effect on the adhesion to fibronectin, type I collagen and laminin. Similarly, the forced expression of syntenin to human gastric cancer cell line Az521 increased its migratory and invasive potential in vitro. Syntenin-expressing MCF7 cells were associated with the appearance of numerous cell surface extensions and with pseudopodia formation on collagen I, suggesting that syntenin may be involved in the signaling cascade to actin-reorganization. Mutation study suggested that PDZ2 domain of syntenin could be an essential role in its stimulatory effect on the cell migration. This is the first demonstration that syntenin, a PDZ motif-containing protein, can be overexpressed during the metastatic progression of human breast and gastric cancer cells and that it can function as a metastasis-inducing gene.
Koo
Tae Hyeon
TH
Anti-Cancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, P.O. Box 115, Yuseong, Daejeon 305-600, Korea.
Lee
Jung-Joon
JJ
Kim
Eun-Mi
EM
Kim
Kyu-Won
KW
Kim
Han Do
HD
Lee
Jeong-Hyung
JH
D001483:Base Sequence; D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D017931:DNA Primers; D020869:Gene Expression Profiling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D053676:Syntenins; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C109621:SDCBP protein, human; D053676:Syntenins