title: S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells.
abstract: S100A4, a member of the Ca(2+) dependent S100 protein family, is reported to associate with metastasis through regulation of the motility and invasiveness of cancer cells. A high level of S100A4 protein has been reported in a variety of cancers, including pancreatic cancer. However, its biological role in pancreatic carcinogenesis is largely unknown. We previously reported that S100A4 is frequently overexpressed and that RNAi-mediated knockdown induces apoptosis and suppression of cell growth, motility, and invasiveness. In this study, we analyzed the effects of forced expression of S100A4 in pancreatic cancer cell lines without S100A4-upregulation. We used two cell lines without upregulation of S100A4 (PCI-35 and PCI-43) as well as two cell lines with highly upregulated S100A4 as the control (MIA PaCa-2 and PAN-07-JCK). Cells did not show acceleration of their growth and invasiveness after forced expression of S100A4, but remarkable acceleration of cell motility was observed only in PCI-35 and PCI-43. We further performed microarray analyses using PCI-35 and PCI-43 with and without forced expression of S100A4 and identified 72 and 18 genes that were 2-fold or more upregulated or downregulated, respectively, in both cell lines after forced expression of S100A4. Our results suggest that S100A4 is crucial for cell motility in pancreatic cancer and that some downstream genes may play important roles in cell motility.
authors.affiliation: Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi 980-8575, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Sekine
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Saiki
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshino
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Umetsu
authors.forename: Guo
authors.initials: G
authors.lastname: Jin
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
authors.forename: Zhaodi
authors.initials: Z
authors.lastname: Gu
authors.forename: Shinichi
authors.initials: S
authors.lastname: Fukushige
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Akira
authors.initials: A
authors.lastname: Horii
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009361:Neoplasm Invasiveness; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human