Focusing the Spotlight on the Zebrafish Intestine to Illuminate Mechanisms of Colorectal Cancer

  • Viola H. Lobert
  • Dmitri Mouradov
  • Joan K. HeathEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 916)


Colorectal cancer, encompassing colon and rectal cancer, arises from the epithelial lining of the large bowel. It is most prevalent in Westernised societies and is increasing in frequency as the world becomes more industrialised. Unfortunately, metastatic colorectal cancer is not cured by chemotherapy and the annual number of deaths caused by colorectal cancer, currently 700,000, is expected to rise. Our understanding of the contribution that genetic mutations make to colorectal cancer, although incomplete, is reasonably well advanced. However, it has only recently become widely appreciated that in addition to the ongoing accumulation of genetic mutations, chronic inflammation also plays a critical role in the initiation and progression of this disease. While a robust and tractable genetic model of colorectal cancer in zebrafish, suitable for pre-clinical studies, is not yet available, the identification of genes required for the rapid proliferation of zebrafish intestinal epithelial cells during development has highlighted a number of essential genes that could be targeted to disable colorectal cancer cells. Moreover, appreciation of the utility of zebrafish to study intestinal inflammation is on the rise. In particular, zebrafish provide unique opportunities to investigate the impact of genetic and environmental factors on the integrity of intestinal epithelial barrier function. With currently available tools, the interplay between epigenetic regulators, intestinal injury, microbiota composition and innate immune cell mobilisation can be analysed in exquisite detail. This provides excellent opportunities to define critical events that could potentially be targeted therapeutically. Further into the future, the use of zebrafish larvae as hosts for xenografts of human colorectal cancer tissue, while still in its infancy, holds great promise that zebrafish could one day provide a practical, preclinical personalized medicine platform for the rapid assessment of the metastatic potential and drug-sensitivity of patient-derived cancers.


Zebrafish Intestinal epithelium Colon cancer Colorectal cancer WNT signalling Intestinal permeability Microbiota Inflammatory bowel disease 



The authors are immensely grateful to Drs Michael Christie, Jan Spitsbergen, Adam Parslow and Elizabeth Christie for kindly providing the images for Figs. 1, 3 and 4. Drs Karen Guillemin, Tanya de Jong-Curtain and Fansuo Geng are thanked for careful reading of the manuscript. Research in the Heath laboratory is supported by the National Health and Medical Research Council of Australia, Ludwig Cancer Research and operational infrastructure grants from the Australian Federal Government (IRISS) and the Victorian State Government (OIS). JKH wishes to thank all past and present members of her laboratory for contributing data and stimulating discussions on this topic over the past several years.


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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Viola H. Lobert
    • 1
    • 2
  • Dmitri Mouradov
    • 3
  • Joan K. Heath
    • 1
    • 4
    Email author
  1. 1.Development and Cancer DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  2. 2.Department of Biochemistry, Institute for Cancer ResearchOslo University Hospital, MontebelloOsloNorway
  3. 3.Systems Biology and Personalised Medicine DivisionThe Walter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  4. 4.Department of Medical BiologyUniversity of MelbourneParkvilleAustralia

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