Arhgef11, also known as PDZ-RhoGEF, is a Rho-guanine nucleotide exchange factor. It is a specific guanine nucleotide exchange factor (GEF) for RhoA, playing a crucial role in regulating actin cytoskeleton dynamics. It is involved in multiple pathways such as the β-catenin pathway, Rho-ROCK pathway, and is associated with various biological processes like cell migration, epithelial-mesenchymal transition (EMT), and the maintenance of epithelial tight junctions [1,3,4,5].

In HCC, knockdown of ARHGEF11 inhibited cell proliferation and invasion, and attenuated β-catenin nuclear translocation, repressing EMT and causing cell cycle arrest [1]. In the Dahl salt-sensitive rat, loss of Arhgef11 protected against hypertension-induced renal injury, with early transcriptome/protein changes in the cytoskeleton [2]. Depletion of Arhgef11 in mammalian cells reduced Rho GTPase activity crosstalk, cell protrusion-retraction dynamics, and migration distance [3]. Ablation of Esrp1/2 led to loss of the epithelial isoform of Arhgef11, impairing epithelial tight junction integrity [4].

In conclusion, Arhgef11 is essential for various cellular functions including cell migration, EMT, and maintaining epithelial tight junctions. Research using gene-knockout models, such as in rats, has revealed its significant role in diseases like hepatocellular carcinoma and hypertension-induced renal injury, providing valuable insights into the underlying molecular mechanisms and potential therapeutic targets.