PUBLICATION

Impaired light detection of the circadian clock in a zebrafish melanoma model

Authors
Hamilton, N., Diaz-de-Cerio, N., Whitmore, D.
ID
ZDB-PUB-150403-7
Date
2015
Source
Cell cycle (Georgetown, Tex.)   14(8): 1232-41 (Journal)
Registered Authors
Keywords
Cancer, Cell cycle, Circadian clock, Light input, Melanoma, Zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified/metabolism
  • Circadian Clocks/genetics
  • Circadian Clocks/physiology*
  • Cryptochromes/genetics
  • Cryptochromes/metabolism
  • Cyclin B1/genetics
  • Cyclin B1/metabolism
  • DNA Damage
  • DNA Repair
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism
  • Disease Models, Animal
  • Eye Proteins/genetics
  • Eye Proteins/metabolism
  • Light*
  • Melanoma/metabolism
  • Melanoma/pathology*
  • Microphthalmia-Associated Transcription Factor/deficiency
  • Microphthalmia-Associated Transcription Factor/genetics
  • Microphthalmia-Associated Transcription Factor/metabolism
  • Period Circadian Proteins/genetics
  • Period Circadian Proteins/metabolism
  • S Phase
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
25832911 Full text @ Cell Cycle
Abstract
The circadian clock controls the timing of the cell cycle in healthy tissues and clock disruption is known to increase tumourigenesis. Melanoma is one of the most rapidly increasing forms of cancer and the precise molecular circadian changes that occur in a melanoma tumour are unknown. Using a melanoma zebrafish model, we have explored the molecular changes that occur to the circadian clock within tumours. We have found disruptions in melanoma clock gene expression due to a major impairment to the light input pathway, with a parallel loss of light-dependent activation of DNA repair genes. Furthermore, the timing of mitosis in tumours is perturbed, as well as the regulation of certain key cell cycle regulators, such that cells divide arhythmically. The inability to co-ordinate DNA damage repair and cell division is likely to promote further tumourigenesis and accelerate melanoma development.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping