RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells.
S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca(2+)-binding proteins, and overexpression of S100A4 is suggested to associate with cell proliferation, invasion, and metastasis. We observed frequent overexpression of S100A4 in pancreatic cancer cell lines and further analyzed RNAi-mediated knockdown to address the possibility of its use as a therapeutic target for pancreatic cancer. The specific knockdown of S100A4 strongly suppressed cell growth, induced G2 arrest and eventual apoptosis, and decreased cell migration. Furthermore, microarray analyses revealed that knockdown of S100A4 induced expression of the tumor suppressor genes PRDM2 and VASH1. Our present results suggest the possibility that the inhibition of S100A4 can be utilized in antitumor applications for patients with pancreatic cancer.
Tabata
Takahiro
T
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
Tsukamoto
Nobukazu
N
Fooladi
Abbas Ali Imani
AA
Yamanaka
Sumitaka
S
Furukawa
Toru
T
Ishida
Masaharu
M
Sato
Daisuke
D
Gu
Zhaodi
Z
Nagase
Hiroki
H
Egawa
Shinichi
S
Sunamura
Makoto
M
Horii
Akira
A
D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014157:Transcription Factors; C493181:VASH1 protein, human; C077591:S100A4 protein, human; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human