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RNA interference targeting against S100A4 suppresses cell growth and motility and induces apoptosis in human pancreatic cancer cells
Authors:Takahiro Tabata  Abbas Ali Imani Fooladi  Toru Furukawa  Daisuke Sato  Hiroki Nagase  Makoto Sunamura  Akira Horii
Institution:a Department of Molecular Pathology, Tohoku University School of Medicine, Sendai Miyagi 980-8575, Japan
b Department of Gastroenterological Surgery, Tohoku University School of Medicine, Sendai Miyagi 980-8575, Japan
c Cancer Surgery Section, Hammersmith Hospital, Imperial College, London, UK
d Division of Cancer Genetics, Department of Advanced Medical Science, Nihon University School of Medicine, Itabashi, Tokyo 173-8610, Japan
Abstract:S100A4 protein belongs to the S100 subfamily, which has grown to be one of the large subfamilies of the EF-hand Ca2+-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.
Keywords:Invasion  Pancreatic cancer  PRDM2  RNAi  S100A4  VASH1
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