Metastasis is the main cause of
cancer-associated deaths, yet this complex process is still not well understood. Many studies have shown that
acetate is involved in
cancer metastasis, but the molecular mechanisms remain to be elucidated. In the present study, we first measured the effect of
acetate on zinc finger transcriptional repressor SNAI1 and
acetyl-CoA synthetase 2 (ACSS2) under
glucose limitation in
renal cell carcinoma cell lines, 786-O and ACHN. Then, RNA interference and overexpression of ACSS2 were used to detect the role of
acetate on SNAI1 expression and cell migration. Finally,
chromatin immunoprecipitation assay (ChIP) was used to investigate the regulatory mechanism of
acetate on SNAI1 expression. The results showed that
acetate increased the expressions of SNAI1 and ACSS2 under
glucose limitation. ACSS2 knockdown significantly decreased
acetate-induced SNAI1 expression and cell migration, whereas overexpression of ACSS2 increased SNAI1 level and
histone H3K27 acetylation (H3K27ac). ChIP results revealed that
acetate increased H3K27ac levels in regulatory region of SNAI1, but did not increase ACSS2-binding ability. Our study identified a novel inducer,
acetate, which can promote SNAI1 expression by ACSS2-mediated
histone acetylation in partly. This finding has important implication in treatment of metastatic
cancers.