G9a and histone deacetylases are crucial for Snail2‐mediated E‐cadherin repression and metastasis in hepatocellular carcinoma

摘要

Functional E‐cadherin loss, a hallmark of epithelial‐mesenchymal transition ( ), is important for metastasis. However, the mechanism of Snail2 in hepatocellular carcinoma ( ) and metastasis remains unclear. Here, we showed that Snail2 was upregulated in primary , and significantly increased during transforming growth factor‐β‐induced liver cell . Snail2‐overexpressing and knockdown cell lines have been established to determine its function in in . H3K9 methylation was upregulated and H3K4 and H3K56 acetylation were downregulated at the E‐cadherin promoter in Snail2‐overexpressing cancer cells. Furthermore, Snail2 interacted with G9a and histone deacetylases ( s) to form a complex to suppress E‐cadherin transcription. Snail2 overexpression enhanced migration and invasion in cells, whereas G9a and inhibition significantly reversed this effect. Moreover, Snail2 overexpression in cancer cells increased tumor metastasis and shortened survival time in mice, whereas G9a and inhibitors extended survival. Our study not only reveals a critical mechanism underlying the epigenetic regulation of but also suggests novel treatment strategies for .