Negative Regulation of CDH1 Gene Transcription

Transcription factors implicated in direct repression of CDH1 gene transcription by a single study are not shown in the pathway diagram. These include AR, SOX30, GATA1, MIER3, TBX3, KLF8, and GRHL3.

Hepatitis B virus (HBV)-encoded X antigen (HBx) downregulates CDH1 gene transcription by recruiting the SIN3A:HDAC histone deacetylase complex to the Snail-binding sites in the human CDH1 gene promoter. Hepatitis C virus (HCV) core protein facilitates binding of SNAI1 to the CDH1 gene promoter and the consequent downregulation of CDH1 gene transcription. Hexavalent chromium Cr(VI), a carcinogen associated with lung diseases and lung cancer, represses CDH1 gene expression through activation of CDH1 gene repressors such as SNAI1, ZEB1, and KLF8, and enhancing the binding of HDAC1 to the CDH1 gene promoter.

Downregulation of the CDH1 gene expression is one of the hallmarks of epithelial-to-mesenchymal transition, seen normally during development and wound healing, but also pathologically, during cancer progression (reviewed in Serrano-Gomez et al. 2016). Expression of many negative regulators of the CDH1 gene is controlled by TGF-beta signaling, prostaglandin E(2) signaling, WNT signaling, and NFκB signaling.