Downregulation of S100A4 expression by RNA interference suppresses cell             growth and invasion in human colorectal cancer cells.
S100A4 protein, a member of the S100 superfamily of calcium-binding proteins,             is frequently observed in various types of human cancers, including colorectal             cancer (CRC). Our previous investigations have demonstrated that the overexpression             of S100A4 is associated with lymph node metastasis and poor prognosis in CRC;             however, its biological roles in CRC remain unclear. In the present study, we             compared the expression of S100A4 at the mRNA and protein levels in six CRC cell             lines, and found that the expression levels roughly coincided with their invasiveness.             Using RNA interference, we suppressed S100A4 expression in SW620 CRC cells with             highly invasive potential and S100A4 high expression. The specific knockdown of             S100A4 strongly suppressed cell growth, migration and invasion activities. Furthermore,             employing metastasis-related gene mRNA microarrays, we found four genes to be             significantly dysregulated (more than 2-fold) after downregulation of S100A4,             including three downregulated genes (MMP9, MMP10 and CDH11) and one upregulated             gene (TIMP4). Our present results indicate that S100A4 may positively regulate             tumor cell proliferation, invasion and metastasis associated with multiple molecules.             Thus, the inhibition of S100A4 might be a potentially novel approach to treatment             for CRC.
Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.
Liyong
L
Huang
Ye
Y
Xu
Guoxiang
G
Cai
Zuqing
Z
Guan
Sanjun
S
Cai
D015820:Cadherins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053506:Matrix Metalloproteinase 10 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
D015820:Cadherins; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; C086960:osteoblast cadherin; C511770:MMP10 protein, human; D053506:Matrix Metalloproteinase 10; D020780:Matrix Metalloproteinase 9