Capza1-flox Mouse

Capza1, also known as capping actin protein of muscle Z-line alpha subunit 1, is a key component of the capping protein complex CapZ which binds to actin filaments. It plays a vital role in regulating actin cytoskeleton remodelling, an essential process in maintaining cell morphology, movement, and cellular phenotypes. The regulation of actin filament assembly by Capza1 is involved in multiple biological pathways such as epithelial-mesenchymal transition (EMT) [4,7,8].

In various cancers, Capza1 shows diverse roles. In lung adenocarcinoma (LUAD), higher Capza1 expression has an unfavourable prognostic value and is associated with immune infiltration cells, immune markers, and immune checkpoints, suggesting it as a potential immunological therapeutic target [1]. In non-small cell lung cancer, Capza1 is low-expressed and contributes to tumor cell proliferation and metastasis [2]. In gastric cancer, Capza1 overexpression is associated with well-differentiated histology, smaller tumor size, and longer survival time, and in vitro, its overexpression decreases cell migration and invasion [9]. In hepatocellular carcinoma (HCC), Capza1 inhibits EMT and intrahepatic metastases by regulating actin cytoskeleton remodelling, and its expression levels are negatively correlated with the biological characteristics of primary HCC and patient prognosis [4]. Also, FAM21C in HCC can promote invasion and migration by inhibiting the capping ability of Capza1 [7], and hypoxia in HCC can regulate the binding of Capza1 to F-actin via PIP2 to drive EMT [8]. Moreover, in Helicobacter pylori-infected gastric epithelial cells, Capza1 inhibits autolysosome formation by preventing LRP1-ICD from binding to the LAMP1 promoter, increasing the risk of gastric carcinogenesis, and Helicobacter pylori-infected CAPZA1-overexpressing cells can give rise to CD44v9-positive cancer stem-like cells [3,5]. Additionally, polymorphisms in Capza1 may be associated with the development of gastric mucosal atrophy [6]. Exosome-delivered circSTAU2 in gastric cancer can inhibit progression by targeting the miR-589/Capza1 axis [10].

In conclusion, Capza1 is crucial in regulating actin cytoskeleton remodelling, which impacts various biological processes and disease conditions, especially in multiple cancer types. Studies on Capza1 contribute to understanding cancer development mechanisms, providing potential prognostic and therapeutic targets for cancers like LUAD, non-small cell lung cancer, gastric cancer, and HCC, as well as for gastric mucosal atrophy related to Helicobacter pylori infection.