The S100A4 D10V polymorphism is related to cell migration ability but not drug resistance in gastric cancer cells

Tein Ming Yuan, Ruei Yue Liang, Nai Wan Hsiao, Show Mei Chuang

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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.

Original languageEnglish
Pages (from-to)2307-2318
Number of pages12
JournalOncology Reports
Volume32
Issue number6
DOIs
Publication statusPublished - 2014 Dec 1

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Drug Resistance
Stomach Neoplasms
Cell Movement
Cell Survival
Pharmaceutical Preparations
Annexin A2
Neoplasm Metastasis
Viperidae
RNA Interference
Single Nucleotide Polymorphism
Neoplasms
Up-Regulation
Cell Proliferation
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Yuan, Tein Ming ; Liang, Ruei Yue ; Hsiao, Nai Wan ; Chuang, Show Mei. / The S100A4 D10V polymorphism is related to cell migration ability but not drug resistance in gastric cancer cells. In: Oncology Reports. 2014 ; Vol. 32, No. 6. pp. 2307-2318.
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The S100A4 D10V polymorphism is related to cell migration ability but not drug resistance in gastric cancer cells. / Yuan, Tein Ming; Liang, Ruei Yue; Hsiao, Nai Wan; Chuang, Show Mei.

In: Oncology Reports, Vol. 32, No. 6, 01.12.2014, p. 2307-2318.

Research output: Contribution to journalArticle

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