PUBLICATION
Cdc6 cooperates with c-Myc to promote genome instability and EMT in zebrafish
- Authors
- Chen, C.H., Lin, D.S., Cheng, C.W., Lin, C.J., Lo, Y.K., Yen, C.C., Lee, A.Y., Hsiao, C.D.
- ID
- ZDB-PUB-140723-1
- Date
- 2014
- Source
- Oncotarget 5(15): 6300-11 (Journal)
- Registered Authors
- Hsiao, Chung-Der
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cell Cycle Proteins/genetics*
- Cell Cycle Proteins/metabolism
- Epithelial-Mesenchymal Transition/genetics*
- Genes, myc*
- Genomic Instability*
- Humans
- Nuclear Proteins/genetics*
- Nuclear Proteins/metabolism
- Zebrafish
- PubMed
- 25051368 Full text @ Oncotarget
Citation
Chen, C.H., Lin, D.S., Cheng, C.W., Lin, C.J., Lo, Y.K., Yen, C.C., Lee, A.Y., Hsiao, C.D. (2014) Cdc6 cooperates with c-Myc to promote genome instability and EMT in zebrafish. Oncotarget. 5(15):6300-11.
Abstract
Aberration in DNA replication is a major cause to genome instability that is a hallmark of cancer cells. Cell division cycle 6 (Cdc6) and c-Myc have a critical role in the initiation of DNA replication. However, whether their interaction induces epithelial-mesenchymal transition (EMT) and promotes tumorigenesis in in vivo animal model remains unclear. Since using zebrafish as a cancer model has been restricted by the late onset of tumorigenesis and extreme difficulty in transformation on skin, we tried to establish a novel non-melanoma skin model in zebrafish to study their role in tumorigenesis. A stable transgenic zebrafish was created by using tol2 transposon, in which cdc6 and c-myc were co-overexpressed in epidermis driven by a skin-specific krt4 promoter. Intriguingly, co-overexpression of cdc6 and c-myc in transgenic zebrafish skin triggered tumor-like transformation, apoptosis attenuation, genomic instability, and EMT, hallmarks of malignant tumorigenesis. Our findings and other characteristics of zebrafish, including optical clarity and small molecule treatment, provide the future utility of this model for easy and non-invasive detection and for identification of new anti-cancer drug.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping