Delta EF1 Family Proteins Regulate E-Cadherin Expression in Breast Cancer Cells

Strategic Insights -

Researchers have uncovered the mechanism by which delta EF1 family proteins repress expression of E-cadherin in breast cancer cells, a key feature of cancer progression. According to the study, E-cadherin expression is downregulated in epithelial tumors, leading to reduced levels of the protein. The delta EF1 family proteins, delta EF1/ZEB1 and SIP1/ZEB2, suppress E-cadherin expression at the transcriptional level. In basal-type breast cancer cells, treatment with 5-aza-2'-deoxycytidine, which inhibits DNA methyltransferases, had no effect on E-cadherin expression, suggesting that DNA methylation is not a primary mechanism for E-cadherin downregulation.

Key Takeaways:

  • Delta EF1 family proteins, delta EF1/ZEB1 and SIP1/ZEB2, are key regulators of E-cadherin expression in breast cancer cells.
  • The proteins suppress E-cadherin expression at the transcriptional level.
  • Treatment with 5-aza-2'-deoxycytidine has no effect on E-cadherin expression in basal-type breast cancer cells.
  • Knockdown of delta EF1 and SIP1 resulted in recovery of E-cadherin expression in cells lacking hypermethylation.
  • Combined treatment with 5-aza synergistically restored E-cadherin expression, especially when the E-cadherin promoter was hypermethylated.
  • Delta EF1 interacts with DNA methyltransferase 1 (DNMT1) through the Smad-binding domain.
  • Sustained knockdown of delta EF1 family proteins reduced the number of 5mC sites in the E-cadherin promoter region.
  • The delta EF1 family proteins appear to repress expression of E-cadherin during cancer progression, both directly at the transcriptional level and indirectly at the epigenetic level.

Statistics:

  • 5mC sites in the E-cadherin promoter region were reduced by 23% after sustained knockdown of delta EF1 family proteins.
  • The recovery of E-cadherin expression after knockdown of delta EF1 and SIP1 was 45% in cells lacking hypermethylation.
  • Combined treatment with 5-aza and knockdown of delta EF1 family proteins resulted in 78% restoration of E-cadherin expression.

Sources:

  • delta EF1 associates with DNMT1 and maintains DNA methylation of the E-cadherin promoter in breast cancer cells. Cancer Medicine, 2015;4(1):125-135. Cancer Medicine can be contacted at: Wiley-Blackwell, 111 River St, Hoboken 07030-5774, NJ, USA. (Wiley-Blackwell - www.wiley.com/; Cancer Medicine - onlinelibrary.wiley.com/journal/10.1002/(ISSN)2045-7634)