Dishevelled-associated antagonist of
beta-catenin 2 (Dact2) is involved in the regulation of intracellular signaling pathways during development. It negatively regulates the Nodal signaling pathway, possibly by promoting lysosomal degradation of Nodal receptors such as
TGFBR1, and plays an inhibitory role during the re-epithelialization of skin
wounds by attenuating
transforming growth factor-β signaling. Dact2 is known to act as a functional
tumor suppressor in
colon cancer; reduced Dact2 can promote
liver cancer progression and suppress
gastric cancer proliferation, invasion, and
metastasis by inhibiting Wnt signaling. Zebrafish is used as a model of
cancer biology because it shows similar
tumorigenesis and morphogenesis as in humans and gene manipulation in this organism is possible. This study was performed to explore phenotypic changes in Dact2 knockout zebrafish and investigate the function of Dact2. A 10-base pair deletion Dact2 knockout zebrafish was prepared using the CRISPR-Cas9 genome editing system. Dact2 knockout enhanced the expression of the MMP2 and MMP9 genes, which are related to
tumor invasion and migration, and the Snail,
VEGF, and ZEB genes, which are related to epithelial-mesenchymal transition (EMT). The absence of Dact2 also resulted in
hyperplasia of the gastrointestinal epithelium,
fibrosis in the pancreas and liver, increased proliferation of the pancreatic and hepatic bile ducts, and invasive proliferation into the pancreas. A wound healing assay confirmed that the absence of Dact2 enhanced EMT, thus accelerating wound healing. This study suggests that a loss of function of Dact2 impacts EMT-related gene regulation and
tumor generation in a zebrafish knockout model, which is a useful model for exploring the mechanisms of these processes.