Epigenetic suppression of E-cadherin expression by Snail2 during the metastasis of colorectal cancer

Clin Epigenetics. 2018 Dec 12;10(1):154. doi: 10.1186/s13148-018-0592-y.


Background: The transcription factor Snail2 is a repressor of E-cadherin expression during carcinogenesis; however, the specific mechanisms involved in this process in human colorectal cancer (CRC) remain largely unknown.

Method: We checked the expression of Snail2 in several clinical CRC specimens. Then, we established Snail2-overexpressing and knockdown cell lines to determine the function of Snail2 during EMT and metastasis processes in CRC. In addition, we used luciferase reporter assay to explore how Snail2 inhibits the expression of E-cadherin and induces EMT.

Results: We found that the expression of Snail2 was higher in clinical specimens of colorectal cancer (CRC) compared to non-cancerous tissues. Overexpression of Snail2 induced migration and metastatic properties in CRC cells in vitro and in vivo. Furthermore, overexpression of Snail2 promoted the occurrence of the epithelial-mesenchymal transition (EMT), downregulating the expression of E-cadherin and upregulating that of vimentin. Specifically, Snail2 could interact with HDAC6 and then recruited HDAC6 and PRC2 to the promoter of E-cadherin and thus inhibited the expression of E-cadherin, promoting EMT and inducing invasion and metastasis of CRC.

Conclusion: Our study reveals that Snail2 might epigenetically suppress the expression of E-cadherin during CRC metastasis.

Keywords: Colorectal cancer; E-cadherin; EZH2; HDAC6; Metastasis; Snail2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics*
  • Cadherins / genetics*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Epigenesis, Genetic
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase 6 / metabolism
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Liver Neoplasms / secondary*
  • Mice
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Polycomb Repressive Complex 2 / metabolism
  • Promoter Regions, Genetic
  • Signal Transduction
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism*
  • Up-Regulation


  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Polycomb Repressive Complex 2
  • HDAC6 protein, human
  • Histone Deacetylase 6