Cdh1-flox Mouse

Cdh1, which encodes E-cadherin, is a crucial gene as E-cadherin is a key protein in adherens junctions. It is involved in major cellular processes such as embryogenesis and maintenance of tissue architecture, and is recognized as a tumour suppressor gene [6].

Pathogenic CDH1 germline mutations are associated with lobular breast cancer in the hereditary lobular breast cancer (HLBC) syndrome, and also with the hereditary diffuse gastric cancer (HDGC) syndrome. A higher frequency of CDH1 mutations was identified in the HLBC syndrome with an early age at LBC diagnosis, and inactivating CDH1 mechanisms (second hit) were found in some tumor samples of germline CDH1 variant carriers [1,2]. In families with the HDGC syndrome, CDH1 splicing and missense germline mutations occur with higher frequency in healthy subjects than in patients with gastric cancer, suggesting not all pathogenic CDH1 germline mutations confer the same cancer-developing risk [3]. Also, young women carrying germline CDH1 variants have a relatively high frequency of diffuse gastric cancer in the HDGC syndrome [4]. High CDH1 methylation is significantly associated with an increased risk of esophageal cancer, and it can potentially serve as a diagnostic marker [5]. Germline CDH1 defects are related to the development of multiple cancers, including gastric, breast, prostate, and colorectal cancers [7]. In triple-negative breast cancer (TNBC), high levels of Cdh1 expression are correlated with poor prognoses, and interfering with Cdh1 function can potentiate the cytotoxic effects of PARP inhibitors [8].

In conclusion, Cdh1 is essential for maintaining normal cellular functions and tissue architecture. Studies on CDH1 germline mutations have revealed its significant role in the development of various cancers, including lobular breast cancer, diffuse gastric cancer, and esophageal cancer, as well as its potential as a target for TNBC treatment. Understanding Cdh1 through genetic models helps in uncovering disease mechanisms and developing preventive and treatment strategies for related cancers.