Review Article | Published:

Drosophila melanogaster: a model and a tool to investigate malignancy and identify new therapeutics

Nature Reviews Cancer volume 13, pages 172183 (2013) | Download Citation

Abstract

For decades, lower-model organisms such as Drosophila melanogaster have often provided the first glimpse into the mechanism of action of human cancer-related proteins, thus making a substantial contribution to elucidating the molecular basis of the disease. More recently, D. melanogaster strains that are engineered to recapitulate key aspects of specific types of human cancer have been paving the way for the future role of this 'workhorse' of biomedical research, helping to further investigate the process of malignancy, and serving as platforms for therapeutic drug discovery.

Key points

  • For a century, seemingly non-applied research carried out in Drosophila melanogaster has provided the first glimpse into the mechanism of action of human cancer-related proteins.

  • Natural malignant tumours can occur in D. melanogaster.

  • Tumours can also be experimentally induced in larvae and adult flies either by knocking down fly tumour suppressor genes or by recreating in flies the mutant conditions that are causative of certain human cancer types. Current examples of this 'a la carte' design include cancer models of glioblastoma, rhabdomyosarcoma, multiple endocrine neoplasia and leukaemia.

  • D. melanogaster tumours range from hyperplasias to frankly malignant neoplasias that are invasive and lethal to the host.

  • Both the presence and the lack of supernumerary centrosomes can cause tumours in the larval brain, but unbalanced karyotypes do not. Thus, in D. melanogaster, Boveri's hypothesis does not apply, but centrosome dysfunction is linked to cancer.

  • The origin of the widespread genome instability that is characteristic of cancer cells is likely to be multifactorial.

  • The loss of cell polarity in cells that divide asymmetrically, as well as in epithelial tissues, is often tumorigenic.

  • The Aurora and POLO protein kinases are tumour suppressors in the larval brain.

  • The activation of signalling pathways that sense low calorie intake and inhibit target of rapamycin (TOR) compromises cortical polarity and contributes to tumour growth.

  • Data derived from D. melanogaster strongly substantiate the view that timely repression of gene expression programmes during development has a pronounced tumour suppression function.

  • D. melanogaster lethal (3) malignant brain tumour (l(3)mbt) tumours recapitulate the ectopic expression of cancer germline (CG; also known as cancer testis (CT)) genes that are observed in many types of somatic human tumours. In D. melanogaster, inactivation of some CG genes inhibits tumour growth.

  • D. melanogaster is starting to have an important role in chemical genetics, helping to identify the pathways that are affected by current pharmaceuticals, facilitating the design of more efficient derivatives and serving as a platform for semi-automated screens for new anticancer drugs.

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Acknowledgements

The author is very grateful to T. T. Su, Y. Zheng, S. Llamazares, E. Scheenaard, J. Januschke, J. Reina, F. Rossi, J. Petrovic, J. Pampalona and G. Pollarollo for critical reading of the manuscript. Research in the author's laboratory is funded by grants BFU2009-07975/BMC, BFU2012-32522, CENIT ONCOLOGICA-20091016, SGR Agaur 2009 CG041413 and ERC-2011-AdG 294603.

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  1. IRB-Barcelona, c/Baldiri Reixac 10–12, Barcelona, Spain. Institucio Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, Barcelona, Spain.

    • Cayetano Gonzalez

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The author declares no competing financial interests.

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Correspondence to Cayetano Gonzalez.

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DOI

https://doi.org/10.1038/nrc3461