S100A4 cooperates with HIF-1 to regulate migration and invasion of gastric can-cer cells via WNT/β-catenin pathway
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Abstract:
Objective: To explore the effects of S100A4 on the migration and invasion capacity of gastric cancer SGC-7901 cells under hypoxia condition, and to identify the possible mechanism; Methods: The gastric cancer cell line, SGC-7901 was transfected with chemically synthesized si-S100A4 plasmidand si-control plasmid (negative control). Depend-ing on the different culture conditions, SGC-7901 cells were further divided into four groups: normoxia (Nor)+si-S100A4 group, Nor+si-Ctrl group, hypoxia(Hyp) + si-Ctrl group and Hyp+si-S100A4 group. Under the hypoxia condition, the pro-tein expressions of HIF-1 and S100A4 in SGC-7901 cells were detected using the Western blotting assay. The effects of si-S100A4 on the expression of S100A4, β-catenin and TCF-4 upon hypoxia condition were further explored. Moreover, the Transwell assay were conducted to explore the effects of hypoxia and si-S100A4 on the migration and invasion capacity of gastric cancer SGC-7901 cells. Results: Under the hypoxia condition, (1) the expression of HIF-1 and S100A4 in gas-tric cancer SGC-7901 cells were significantly up-regulated (3.12±0.23 vs 1.02±0.05,P<0.01; 2.75±0.32 vs 1.05±0.07, P<0.01), and the expressions were significantly correlated (r=0.67,P<0.01); (2) the migration and invasion capacity of SGC-7901 cells were significantly increased (223.31±35.12 vs 131.29±26.40,142.27±26.37,P<0.05]. Under hypoxia+si-S100A4 condition: (1) the promotion effect of hypoxia on the expressions of β-catenin and TCF-4 was significantly re-duced (all P<0.01); (2) the promotion effect of hypoxia on the migration and invasion ability of SGC-7901 cells was sig-nificantly decreased (161.37±31.02 vs 88.21±22.42、95.36±21.29, P<0.05). Conclusion: S100A4 promoted the migration and invasion capacity of gastric cancer SGC-7901 cells, which was possibly achieved by synergistically working with HIF-1 to regulate Wnt/β-catenin pathway.
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Project supported by the Science and Technology Commission Project of Chongqing Yongchuan District (No. Ycstc,2013nc8017)