Background/aims: Several reports have showed the inverse correlation between S100A4 and E-cadherin expression, but the exact molecular mechanism remained unclear. It has been reported that EZH2 mediates transcriptional silencing of E-cadherin by trimethylating lysine 27 of histone H3 (H3K27me3). Therefore, we hypothesized that EZH2 might mediate the inhibition of S100A4 on E-cadherin and further affect the functions of S100A4 in gastric cancer cells.
Methodology: RT-PCR and Western Blot were used to detect the expression of EZH2 and E-cadherin after inhibiting or increasing S100A4 expression. MTT and Transwell assay were performed to detect the proliferation and migration of gastric cancer cells.
Results: Inhibition or overexpression of S100A4 led to decreased or increased EZH2 expression, and increased or decreased E-cadherin expression. The SET domain was important for EZH2 in rescuing the decreased proliferation and migration of the cells after S100A4 inhibition.
Conclusion: As a novel downstream target of S100A4, EZH2 mediates the inhibition of S100A4 on E-cadherin. The SET domain is important for EZH2 in mediating the cellular function of S100A4.