Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Drosophila in cancer research: to boldly go where no one has gone before

Abstract

Transformation and metastasis are complex processes that depend on integration of effects from multiple mutations. Modeling this complexity requires manipulating multiple genes in particular sub-populations of cells in vivo. This is technically challenging in mammalian model systems and has limited the rate of progress in understanding the effects of the complex aberrations present in cancer cells. In contrast, powerful genetic methods in the fruit fly Drosophila allow efficient generation and analysis of complex genotypes in defined cell populations. These methods are already fruitful in exploring the interactions among cancer mutations, and between cell populations that mimic the tumor microenvironment. In this issue of Oncogene, Willecke et al. (2011) describe the implementation of a novel genetic screen in Drosophila to identify genes required for tumor growth in vivo. This report illustrates the power of using Drosophila to perform systematic genome-wide genetic screens in complex genetic backgrounds and for the resulting data to inform our understanding of transformation and metastasis in human systems.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1

References

  • Baker NE . (2007). Patterning signals and proliferation in Drosophila imaginal discs. Curr Opin Genet Dev 17: 287–293.

    CAS  Article  PubMed  Google Scholar 

  • Bier E . (2005). Drosophila, the golden bug, emerges as a tool for human genetics. Nat Rev Genet 6: 9–23.

    CAS  Article  PubMed  Google Scholar 

  • Blair SS . (2003). Genetic mosaic techniques for studying Drosophila development. Development 130: 5065–5072.

    CAS  Article  PubMed  Google Scholar 

  • Brand AH, Perrimon N . (1993). Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415.

    CAS  PubMed  Google Scholar 

  • Brumby AM, Richardson HE . (2003). Scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J 22: 5769–5779.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Brumby AM, Richardson HE . (2005). Using Drosophila melanogaster to map human cancer pathways. Nat Rev Cancer 5: 626–639.

    CAS  Article  PubMed  Google Scholar 

  • Dietzl G, Chen D, Schnorrer F, Su KC, Barinova Y, Fellner M et al. (2007). A genome-wide transgenic RNAi library for conditional gene inactivation in Drosophila. Nature 448: 151–156.

    CAS  Article  PubMed  Google Scholar 

  • Ding L, Ellis MJ, Li S, Larson DE, Chen K, Wallis JW et al. (2010). Genome remodelling in a basal-like breast cancer metastasis and xenograft. Nature 464: 999–1005.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Fortini ME, Skupski MP, Boguski MS, Hariharan IK . (2000). A survey of human disease gene counterparts in the Drosophila genome. J Cell Biol 150: F23–F30.

    CAS  Article  PubMed  Google Scholar 

  • Grewal SS . (2009). Insulin/TOR signaling in growth and homeostasis: a view from the fly world. Int J Biochem Cell Biol 41: 1006–1010.

    CAS  Article  PubMed  Google Scholar 

  • Halder G, Johnson RL . (2011). Hippo signaling: growth control and beyond. Development 138: 9–22.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Humbert PO, Grzeschik NA, Brumby AM, Galea R, Elsum I, Richardson HE . (2008). Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module. Oncogene 27: 6888–6907.

    CAS  Article  PubMed  Google Scholar 

  • Lee T, Luo L . (1999). Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22: 451–-461.

    CAS  Article  PubMed  Google Scholar 

  • Mummery-Widmer JL, Yamazaki M, Stoeger T, Novatchkova M, Bhalerao S, Chen D et al. (2009). Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Nature 458: 987–992.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Neely GG, Hess A, Costigan M, Keene AC, Goulas S, Langeslag M et al. (2010a). A genome-wide Drosophila screen for heat nociception identifies alpha2delta3 as an evolutionarily conserved pain gene. Cell 143: 628–638.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Neely GG, Kuba K, Cammarato A, Isobe K, Amann S, Zhang L et al. (2010b). A global in vivo Drosophila RNAi screen identifies NOT3 as a conserved regulator of heart function. Cell 141: 142–153.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Newsome TP, Asling B, Dickson BJ . (2000). Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127: 851–860.

    CAS  PubMed  Google Scholar 

  • Pagliarini RA, Xu T . (2003). A genetic screen in Drosophila for metastatic behavior. Science 302: 1227–1231.

    CAS  Article  PubMed  Google Scholar 

  • Pan D . (2010). The hippo signaling pathway in development and cancer. Dev Cell 19: 491–505.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Pospisilik JA, Schramek D, Schnidar H, Cronin SJ, Nehme NT, Zhang X et al. (2010). Drosophila genome-wide obesity screen reveals hedgehog as a determinant of brown versus white adipose cell fate. Cell 140: 148–160.

    CAS  Article  PubMed  Google Scholar 

  • Quintana E, Shackleton M, Foster HR, Fullen DR, Sabel MS, Johnson TM et al. (2010). Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized. Cancer Cell 18: 510–523.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, Hariharan IK et al. (2000). Comparative genomics of the eukaryotes. Science 287: 2204–2215.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Schnorrer F, Schonbauer C, Langer CC, Dietzl G, Novatchkova M, Schernhuber K et al. (2010). Systematic genetic analysis of muscle morphogenesis and function in Drosophila. Nature 464: 287–291.

    CAS  Article  PubMed  Google Scholar 

  • St Johnston D . (2002). The art and design of genetic screens: Drosophila melanogaster. Nat Rev Genet 3: 176–188.

    CAS  Article  PubMed  Google Scholar 

  • Willecke M, Toggweiler J, Basler K . (2011). Loss of PI3Kinase blocks cell cycle progression in a Drosophila tumor model. Oncogene 30: 4067–4074.

    CAS  Article  PubMed  Google Scholar 

  • Wu M, Pastor-Pareja JC, Xu T . (2010). Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature 463: 545–548.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  • Xu T, Rubin GM . (1993). Analysis of genetic mosaics in developing and adult Drosophila tissues. Development 117: 1223–1237.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Leisa McCord for art production.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to G Halder.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Halder, G., Mills, G. Drosophila in cancer research: to boldly go where no one has gone before. Oncogene 30, 4063–4066 (2011). https://doi.org/10.1038/onc.2011.128

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2011.128

Further reading

Search

Quick links