title: The S100A4 D10V polymorphism is related to cell migration ability but not drug resistance in gastric cancer cells.
abstract: Upregulation of the metastasis-promoting S100A4 protein has been linked to tumor migration and invasion, and clinical studies have demonstrated that significant expression of S100A4 in primary tumors is indicative of poor prognosis. However, the involvement of S100A4 in the drug responsiveness of gastric cancer remains unclear. In the present study, we used gastric cancer cell lines as a model to investigate the involvement of S100A4 in drug responsiveness. We overexpressed S100A4 in AGS and SCM-1 cells, which are characterized by relatively low-level expression of endogenous S100A4, and found that this significantly enhanced cell migration but did not affect cell survival in the presence of six common anticancer drugs. Moreover, in vitro cell proliferation was unchanged. Using RNA interference, we suppressed S100A4 expression in MKN-45 and TMK-1 cells (which are characterized by high-level expression of endogenous S100A4), and found that knockdown of S100A4 markedly attenuated cell motility but did not affect cell survival in the presence of six common anticancer drugs. Further study revealed that a single nucleotide polymorphism (SNP) of S100A4 (rs1803245; c.29A>T), which substitutes an Asp residue with Val (D10V), is localized within the conserved binding surface for Annexin II. Cells overexpressing S100A4D10V showed a significant reduction in cell migration ability, but no change in cell survival, upon anticancer drug treatment. Taken together, our novel results indicate that the expression level of S100A4 does not significantly affect cell survival following anticancer drug treatment. Thus, depending on the cell context, the metastasis-promoting effects of S100A4 may not be positively correlated with anticancer drug resistance in the clinic.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan, R.O.C.
authors.forename: Tein-Ming
authors.initials: TM
authors.lastname: Yuan
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan, R.O.C.
authors.forename: Ruei-Yue
authors.initials: RY
authors.lastname: Liang
authors.affiliation: Institute of Biotechnology, National Changhua University of Education, Changhua 50007, Taiwan, R.O.C.
authors.forename: Nai-Wan
authors.initials: NW
authors.lastname: Hsiao
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan, R.O.C.
authors.forename: Show-Mei
authors.initials: SM
authors.lastname: Chuang
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D056726:Genetic Association Studies; D006602:Hexosyltransferases; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D020641:Polymorphism, Single Nucleotide; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human; D006602:Hexosyltransferases; C517590:RPN2 protein, human; D046988:Proteasome Endopeptidase Complex