title: Cdc6 cooperates with c-Myc to promote genome instability and epithelial to mesenchymal transition EMT in zebrafish.
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.
authors: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan.
authors: Ching-Hung
authors: CH
authors: Chen
authors: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan; Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan; Mackay Medical College, Taipei, Taiwan.
authors: Dar-Shong
authors: DS
authors: Lin
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors: Chieh-Wen
authors: CW
authors: Cheng
authors: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan.
authors: Chun-Ju
authors: CJ
authors: Lin
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors: Yu-Kang
authors: YK
authors: Lo
authors: Division of Hematology & Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; National Yang-Ming University School of Medicine, Taipei, Taiwan; Therapeutical and Research Center of Musculoskeletal Tumor, Taipei Veterans General Hospital, Taipei, Taiwan.
authors: Chueh-Chuan
authors: CC
authors: Yen
authors: National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan.
authors: Alan Yueh-Luen
authors: AY
authors: Lee
authors: Department of Bioscience Technology, Chung Yuan Christian University, Chung-Li, Taiwan; Center for Nanotechnology, Chung Yuan Christian University, Chung-Li, Taiwan.
authors: Chung-Der
authors: CD
authors: Hsiao
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D016259:Genes, myc; D042822:Genomic Instability; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D015027:Zebrafish
chemical_list: C103706:CDC6 protein, human; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins