CDH1 (also known as E-cadherin, epithelial cadherin, Cadh...

CDH1 (also known as E-cadherin, epithelial cadherin, Cadherin-1, CADH1, or uvomorulin) is a single-membrane-spanning protein with a conserved cytoplasmic domain and five extracellular cadherin domains separated by interdomain Ca2+ binding sites (Gumbiner 2000). Two CDH1 molecules expressed on basolateral membranes of neighboring cells form a homotypic trans-homodimer, a central complex in adherens junctions of polarized epithelia (reviewed in Zhang et al. 2023). CDH1 is connected to the cytoskeleton via its interactions with catenins (reviewed in Zhang et al. 2023).

Loss-of-function missense mutations in CDH1 are an underlying cause of about 30% of cases of hereditary diffuse gastric cancer (HDGC), and they affect various points in CDH1 posttranslational processing, trafficking, and interaction with protein partners (Figueiredo et al. 2013), and a polymorphism in CDH1 gene promoter has also been associated with increased gastric cancer risk (reviewed in Li et al. 2014). CDH1 is frequently downregulated in tumors of epithelial origin and is considered to be a tumor suppressor gene (reviewed in Bruner and Derksen 2018). Loss of CDH1 expression promotes epithelial-to-mesenchymal transition (EMT), implicated in tumor invasiveness (reviewed in Bruner and Derksen 2018). The early stage of EMT is thought to involve removal of CDH1 from the plasma membrane and proteolytic degradation, while the later stage/established EMT is thought to involve repression of CDH1 gene transcription (Janda et al. 2006).

This pathway depicts regulation of CDH1 gene expression at the level of transcription and translation (Reinhold et al. 2010; reviewed in Loh et al. 2019), posttranslational processing and trafficking of CDH1 (reviewed in Zhang et al. 2023), establishment of CDH1 complexes with catenins and homotypic dimers (reviewed in Zhang et al. 2023), and ubiquitin-mediated degradation of CDH1 (reviewed in Zhang et al. 2023).