Cldn7-flox Mouse

Cldn7, also known as claudin 7, is a major component of tight junctions (TJs) [2,4,5,6,7]. TJs play a crucial role in maintaining cell-cell adhesion, and Cldn7 is involved in various biological processes related to cell-cell interactions. It is associated with pathways like the regulation of cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) [1,3,5,6,7].

In colorectal cancer, in vitro and in vivo assays using p53 wild-type CRC cells showed that Cldn7, which is regulated by p53, inhibits cell proliferation [1]. High Cldn7 expression was negatively correlated with tumor size, invasion depth, lymphatic metastasis, and AJCC III/IV stage, and positively associated with favorable prognosis [1].

In breast cancer, database and clinical sample validation indicated that Cldn7 was significantly overexpressed and its overexpression was correlated with poor DFS [3]. TIMER2.0 analysis showed its overexpression was negatively associated with the activation of B-cells, CD4+ T-cells, and CD8+ T-cells, but positively with M0 macrophages [3].

In gastric cancer, Cldn7 was overexpressed, and it promoted cancer cell proliferation, invasion, and EMT [6].

In clear cell renal cell carcinoma (ccRCC), downregulation of Cldn7 due to promoter hypermethylation was associated with cancer progression and poor prognosis, and overexpression of Cldn7 induced cell apoptosis, suppressed proliferation, migration, and invasion of ccRCC cells in vitro and in vivo [7].

In murine breast cancer models, Cldn7 knockdown in organoids induced smooth muscle actin (SMA)-related genes and a mesenchymal phenotype, and Cldn7 was shown to suppress breast cancer invasion and metastasis through negative regulation of SMA-related and mesenchymal gene expression [8].

In conclusion, Cldn7 is a key component of tight junctions that significantly impacts the development and progression of multiple cancers, including colorectal, breast, gastric, and clear cell renal cell carcinomas, as well as breast cancer metastasis. Studies using in vitro and in vivo models, including gene-related functional studies in cancer cells, have revealed its role in regulating cell proliferation, invasion, apoptosis, and EMT, highlighting its potential as a biomarker and therapeutic target in these disease areas.