Cdc6 cooperates with c-Myc to promote genome instability and epithelial to mesenchymal transition (EMT) in zebrafish
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Ching-Hung Chen1, Dar-Shong Lin2,3,4,5, Chieh-Wen Cheng6 , Chun-Ju Lin1, Yu-Kang Lo6, Chueh-Chuan Yen7,8,9, Alan Yueh-Luen Lee6 and Chung-Der Hsiao1,10
1 Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan
2 Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
3 Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan
4 Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
5 Mackay Medical College, Taipei, Taiwan
6 National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
7 Division of Hematology & Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
8 National Yang-Ming University School of Medicine, Taipei, Taiwan
9 Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei, Taiwan
10 Center for Nanotechnology, Chung Yuan Christian University, Chung-Li, Taiwan
Alan Yueh-Luen Lee, email:
Chung-Der Hsiao, email:
Keywords: Cdc6/ c-Myc/ zebrafish /genomic instability/ epithelial to mesenchymal transition
Received: May 24, 2014 Accepted: July 11, 2014 Published: July 11, 2014
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.
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