PUBLICATION
Dact2 is involved in the regulation of epithelial-mesenchymal transition
- Authors
- Kim, D.H., Kim, E.J., Kim, D.H., Park, S.W.
- ID
- ZDB-PUB-200128-11
- Date
- 2020
- Source
- Biochemical and Biophysical Research Communications 524(1): 190-197 (Journal)
- Registered Authors
- Park, Seung Woo
- Keywords
- Dact2, Epithelial-mesenchymal transition, Tumor, Wound healing, Zebrafish
- MeSH Terms
-
- Liver/metabolism
- Liver/pathology
- CRISPR-Cas Systems/genetics
- Zebrafish/genetics
- Carcinogenesis/metabolism
- Carcinogenesis/pathology
- Base Sequence
- Pancreas/pathology
- Epithelial-Mesenchymal Transition*
- Humans
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Gene Expression Regulation
- Gene Knockout Techniques
- Animals
- Wound Healing
- Gastrointestinal Tract/pathology
- PubMed
- 31983425 Full text @ Biochem. Biophys. Res. Commun.
Citation
Kim, D.H., Kim, E.J., Kim, D.H., Park, S.W. (2020) Dact2 is involved in the regulation of epithelial-mesenchymal transition. Biochemical and Biophysical Research Communications. 524(1):190-197.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping