- Adams, M. D. et al. The genome sequence of Drosophila melanogaster. Science 287, 2185–2195 (2000).
Article PubMed Google Scholar
- Rubin, G. M. et al. Comparative genomics of the eukaryotes. Science 287, 2204–2215 (2000).
Article CAS PubMed PubMed Central Google Scholar
- Brumby, A. M. & Richardson, H. E. Using Drosophila melanogaster to map human cancer pathways. Nature Rev. Cancer 5, 626–639 (2005).
Article CAS Google Scholar
- Ellisen, L. W. et al. TAN-1, the human homolog of the Drosophila notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66, 649–661 (1991).
Article CAS PubMed Google Scholar
- Ranganathan, P., Weaver, K. L. & Capobianco, A. J. Notch signalling in solid tumours: a little bit of everything but not all the time. Nature Rev. Cancer 11, 338–351 (2011).
Article CAS Google Scholar
- Pancewicz, J. & Nicot, C. Current views on the role of Notch signaling and the pathogenesis of human leukemia. BMC Cancer 1166, 502 (2011).
Article CAS Google Scholar
- Purow, B. Notch inhibitors as a new tool in the war on cancer: a pathway to watch. Curr. Pharm. Biotechnol. 10, 154–160 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Barakat, M. T., Humke, E. W. & Scott, M. P. Learning from Jekyll to control Hyde: Hedgehog signaling in development and cancer. Trends Mol. Med. 16, 337–348 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Harvey, K. & Tapon, N. The Salvador-Warts-Hippo pathway - an emerging tumour-suppressor network. Nature Rev. Cancer 7, 182–191 (2007).
Article CAS Google Scholar
- Staley, B. K. & Irvine, K. D. Hippo signaling in Drosophila: recent advances and insights. Dev. Dyn. 241, 3–15 (2012).
Article CAS PubMed Google Scholar
- Karpowicz, P., Perez, J. & Perrimon, N. The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration. Development 137, 4135–4145 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Shaw, R. L. et al. The Hippo pathway regulates intestinal stem cell proliferation during Drosophila adult midgut regeneration. Development 137, 4147–4158 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Wadham, C., Gamble, J. R., Vadas, M. A. & Khew-Goodall, Y. The protein tyrosine phosphatase Pez is a major phosphatase of adherens junctions and dephosphorylates β-catenin. Mol. Biol. Cell 14, 2520–2529 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Poernbacher, I., Baumgartner, R., Marada, S. K., Edwards, K. & Stocker, H. Drosophila Pez acts in Hippo signaling to restrict intestinal stem cell proliferation. Curr. Biol. 22, 389–396 (2012).
Article CAS PubMed Google Scholar
- Hanratty, W. P. & Dearolf, C. R. The Drosophila Tumorous-lethal hematopoietic oncogene is a dominant mutation in the hopscotch locus. Mol. Gen. Genet. 238, 33–37 (1993).
CAS PubMed Google Scholar
- Lacronique, V. et al. A TEL-JAK2 fusion protein with constitutive kinase activity in human leukemia. Science 278, 1309–1312 (1997).
Article CAS PubMed Google Scholar
- Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975).
Article CAS PubMed Google Scholar
- Baker, N. E. Cell competition. Curr. Biol. 21, R11–R15 (2011).
Article CAS PubMed Google Scholar
- Johnston, L. A. Competitive interactions between cells: death, growth, and geography. Science 324, 1679–1682 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Morata, G. & Martin, F. A. Cell competition: the embrace of death. Dev. Cell 13, 1–2 (2007).
Article CAS PubMed Google Scholar
- Moreno, E. Is cell competition relevant to cancer? Nature Rev. Cancer 8, 141–147 (2008).
Article CAS Google Scholar
- Chen, C. L., Schroeder, M. C., Kango-Singh, M., Tao, C. & Halder, G. Tumor suppression by cell competition through regulation of the Hippo pathway. Proc. Natl Acad. Sci. USA 109, 484–489 (2012).
Article CAS PubMed Google Scholar
- Lolo, F. N., Casas-Tinto, S. & Moreno, E. Cell competition time line: winners kill losers, which are extruded and engulfed by hemocytes. Cell Rep. 2, 526–539 (2012).
Article CAS PubMed Google Scholar
- Portela, M. et al. Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev. Cell 19, 562–573 (2010).
Article CAS PubMed Google Scholar
- Menendez, J., Perez-Garijo, A., Calleja, M. & Morata, G. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. Proc. Natl Acad. Sci. USA 107, 14651–14656 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Schroeder, M. C., Chen, C. L., Gajewski, K. & Halder, G. A non-cell-autonomous tumor suppressor role for Stat in eliminating oncogenic scribble cells. Oncogene 29 Oct 2012 (doi:10.1038/onc.2012.476).
- Rodrigues, A. B. et al. Activated STAT regulates growth and induces competitive interactions independently of Myc, Yorkie, Wingless and ribosome biogenesis. Development 139, 4051–4061 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Vincent, J. P., Kolahgar, G., Gagliardi, M. & Piddini, E. Steep differences in wingless signaling trigger Myc-independent competitive cell interactions. Dev. Cell 21, 366–374 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Ohsawa, S. et al. Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev. Cell 20, 315–328 (2011). This paper follows tumorigenic events by live microscopy.
Article CAS PubMed Google Scholar
- Cordero, J. B. et al. Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev. Cell 18, 999–1011 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Sunkel, C. E. & Glover, D. M. polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J. Cell Sci. 89, 25–38 (1988).
PubMed Google Scholar
- Glover, D. M., Leibowitz, M. H., McLean, D. A. & Parry, H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 81, 95–105 (1995).
Article CAS PubMed Google Scholar
- Vader, G. & Lens, S. M. The Aurora kinase family in cell division and cancer. Biochim. Biophys. Acta 1786, 60–72 (2008).
CAS PubMed Google Scholar
- Archambault, V. & Glover, D. M. Polo-like kinases: conservation and divergence in their functions and regulation. Nature Rev. Mol. Cell Biol. 10, 265–275 (2009).
Article CAS Google Scholar
- de Carcer, G., Manning, G. & Malumbres, M. From Plk1 to Plk5: functional evolution of polo-like kinases. Cell Cycle 10, 2255–2262 (2011).
Article CAS PubMed PubMed Central Google Scholar
- de Carcer, G., Perez de Castro, I. & Malumbres, M. Targeting cell cycle kinases for cancer therapy. Curr. Med. Chem. 14, 969–985 (2007).
Article CAS PubMed Google Scholar
- Yamashita, Y. M., Jones, D. L. & Fuller, M. T. Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547–1550 (2003).
Article CAS PubMed Google Scholar
- Roberts, D. M., Pronobis, M. I., Poulton, J. S., Kane, E. G. & Peifer, M. Regulation of Wnt signaling by the tumor suppressor adenomatous polyposis coli does not require the ability to enter the nucleus or a particular cytoplasmic localization. Mol. Biol. Cell 23, 2041–2056 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Takacs, C. M. et al. Dual positive and negative regulation of wingless signaling by adenomatous polyposis coli. Science 319, 333–336 (2008).
Article CAS PubMed Google Scholar
- Cheng, L. Y. et al. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell 146, 435–447 (2011).
Article CAS PubMed Google Scholar
- Klovstad, M., Abdu, U. & Schupbach, T. Drosophila brca2 is required for mitotic and meiotic DNA repair and efficient activation of the meiotic recombination checkpoint. PLoS Genet. 466, e31 (2008).
Article CAS Google Scholar
- Thomas, B. J. & Wassarman, D. A. A fly's eye view of biology. Trends Genet. 15, 184–190 (1999).
Article CAS PubMed Google Scholar
- Grzeschik, N. A., Parsons, L. M., Allott, M. L., Harvey, K. F. & Richardson, H. E. Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr. Biol. 20, 573–581 (2010).
Article CAS PubMed Google Scholar
- Poon, C. L., Lin, J. I., Zhang, X. & Harvey, K. F. The sterile 20-like kinase Tao-1 controls tissue growth by regulating the Salvador-Warts-Hippo pathway. Dev. Cell 21, 896–906 (2011).
Article CAS PubMed Google Scholar
- Song, Z., Saghafi, N., Gokhale, V., Brabant, M. & Meuillet, E. J. Regulation of the activity of the tumor suppressor PTEN by thioredoxin in Drosophila melanogaster. Exp. Cell Res. 313, 1161–1171 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Rao, P. R., Makhijani, K. & Shashidhara, L. S. Human APC sequesters β-catenin even in the absence of GSK-3β in a Drosophila model. Oncogene 27, 2488–2493 (2008).
Article CAS PubMed Google Scholar
- Kim, R. H. et al. DJ-1, a novel regulator of the tumor suppressor PTEN. Cancer Cell 7, 263–273 (2005).
Article CAS PubMed Google Scholar
- Martinsson, T. et al. Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumor progression and unresponsiveness to therapy. Cancer Res. 71, 98–105 (2011).
Article CAS PubMed Google Scholar
- Chand, D. et al. Cell and Drosophila model systems define three classes of ALK mutations in neuroblastoma. Dis. Model. Mech. 25 Oct 2012 (doi:10.1242/dmm.010348).
- Pereira, P. S. et al. E-cadherin missense mutations, associated with hereditary diffuse gastric cancer (HDGC) syndrome, display distinct invasive behaviors and genetic interactions with the Wnt and Notch pathways in Drosophila epithelia. Hum. Mol. Genet. 15, 1704–1712 (2006).
Article CAS PubMed Google Scholar
- Caldeira, J. et al. CPEB1, a novel gene silenced in gastric cancer: a Drosophila approach. Gut 61, 1115–1123 (2012).
Article CAS PubMed Google Scholar
- Botham, C. M., Wandler, A. M. & Guillemin, K. A transgenic Drosophila model demonstrates that the Helicobacter pylori CagA protein functions as a eukaryotic Gab adaptor. PLoS Pathog. 466, e1000064 (2008).
Article CAS Google Scholar
- Miles, W. O., Dyson, N. J. & Walker, J. A. Modeling tumor invasion and metastasis in Drosophila. Dis. Model. Mech. 4, 753–761 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Salomon, R. N. & Jackson, F. R. Tumors of testis and midgut in aging flies. Fly 2, 265–268 (2008). This paper describes evidence of natural tumours in flies.
Article PubMed Google Scholar
- Golubovsky, M. D., Weisman, N. Y., Arbeev, K. G., Ukraintseva, S. V. & Yashin, A. I. Decrease in the lgl tumor suppressor dose in Drosophila increases survival and longevity in stress conditions. Exp. Gerontol. 41, 819–827 (2006).
Article CAS PubMed Google Scholar
- Gonzalez, C. Spindle orientation, asymmetric division and tumour suppression in Drosophila stem cells. Nature Rev. Genet. 8, 462–472 (2007).
Article CAS PubMed Google Scholar
- Watson, K. L., Justice, R. W. & Bryant, P. J. Drosophila in cancer research: the first fifty tumor suppressor genes. J. Cell Sci. Suppl. 18, 19–33 (1994).
Article CAS PubMed Google Scholar
- Gateff, E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200, 1448–1459 (1978). This paper identified the first tumour suppressor.
Article CAS PubMed Google Scholar
- Bilder, D. Epithelial polarity and proliferation control: links from the Drosophila neoplastic tumor suppressors. Genes Dev. 18, 1909–1925 (2004).
Article CAS PubMed Google Scholar
- Harris, H., Miller, O. J., Klein, G., Worst, P. & Tachibana, T. Suppression of malignancy by cell fusion. Nature 223, 363–368 (1969).
Article CAS PubMed Google Scholar
- Harris, H. A long view of fashions in cancer research. Bioessays 27, 833–838 (2005).
Article PubMed Google Scholar
- Singh, S. R., Liu, W. & Hou, S. X. The adult Drosophila malpighian tubules are maintained by multipotent stem cells. Cell Stem Cell 1, 191–203 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Zeng, X., Singh, S. R., Hou, D. & Hou, S. X. Tumor suppressors Sav/Scrib and oncogene Ras regulate stem-cell transformation in adult Drosophila malpighian tubules. J. Cell. Physiol. 224, 766–774 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Neumuller, R. A. et al. Genome-wide analysis of self-renewal in Drosophila neural stem cells by transgenic RNAi. Cell Stem Cell 8, 580–593 (2011).
Article PubMed PubMed Central CAS Google Scholar
- Pagliarini, R. A. & Xu, T. A genetic screen in Drosophila for metastatic behavior. Science 302, 1227–1231 (2003).
Article CAS PubMed Google Scholar
- Brumby, A. M. & Richardson, H. E. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 22, 5769–5779 (2003).
Article CAS PubMed PubMed Central Google Scholar
- Wu, M., Pastor-Pareja, J. C. & Xu, T. Interaction between RasV12 and scribbled clones induces tumour growth and invasion. Nature 463, 545–548 (2010). References 65–67 demonstrated cooperative tumorigenesis in D. melanogaster.
Article CAS PubMed PubMed Central Google Scholar
- Elsum, I., Yates, L., Humbert, P. O. & Richardson, H. E. The Scribble-Dlg-Lgl polarity module in development and cancer: from flies to man. Essays Biochem. 53, 141–168 (2012).
Article CAS PubMed Google Scholar
- Pearson, H. B. et al. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J. Clin. Invest. 121, 4257–4267 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Ohsawa, S. et al. Mitochondrial defect drives non-autonomous tumour progression through Hippo signalling in Drosophila. Nature 490, 547–551 (2012). This paper modelled the contribution of mitochondrial dysfunction to tumour growth.
Article CAS PubMed Google Scholar
- Wallace, D. C. Mitochondria and cancer. Nature Rev. Cancer 12, 685–698 (2012).
Article CAS Google Scholar
- Dekanty, A., Barrio, L., Muzzopappa, M., Auer, H. & Milan, M. Aneuploidy-induced delaminating cells drive tumorigenesis in Drosophila epithelia. Proc. Natl Acad. Sci. USA 109, 20549–20554 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Perez-Garijo, A., Shlevkov, E. & Morata, G. The role of Dpp and Wg in compensatory proliferation and in the formation of hyperplastic overgrowths caused by apoptotic cells in the Drosophila wing disc. Development 136, 1169–1177 (2009).
Article CAS PubMed Google Scholar
- Read, R. D., Cavenee, W. K., Furnari, F. B. & Thomas, J. B. A Drosophila model for EGFR-Ras and PI3K-dependent human glioma. PLoS Genet. 566, e1000374 (2009).
Article CAS Google Scholar
- Witte, H. T., Jeibmann, A., Klambt, C. & Paulus, W. Modeling glioma growth and invasion in Drosophila melanogaster. Neoplasia 11, 882–888 (2009). References 74 and 75 used D. melanogaster to model glioblastoma.
Article CAS PubMed PubMed Central Google Scholar
- Wang, Q. et al. Pax genes in embryogenesis and oncogenesis. J. Cell. Mol. Med. 12, 2281–2294 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Galindo, R. L., Allport, J. A. & Olson, E. N. A. Drosophila model of the rhabdomyosarcoma initiator PAX7-FKHR. Proc. Natl Acad. Sci. USA 103, 13439–13444 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Avirneni-Vadlamudi, U. et al. Drosophila and mammalian models uncover a role for the myoblast fusion gene TANC1 in rhabdomyosarcoma. J. Clin. Invest. 122, 403–407 (2012). This paper used D. melanogaster to identify genes involved in rhabdomyosarcomagenesis.
Article CAS PubMed Google Scholar
- Jung, S. H., Evans, C. J., Uemura, C. & Banerjee, U. The Drosophila lymph gland as a developmental model of hematopoiesis. Development 132, 2521–2533 (2005).
Article CAS PubMed Google Scholar
- Martinez-Agosto, J. A., Mikkola, H. K., Hartenstein, V. & Banerjee, U. The hematopoietic stem cell and its niche: a comparative view. Genes Dev. 21, 3044–3060 (2007).
Article CAS PubMed Google Scholar
- Higuchi, M. et al. Expression of a conditional AML1-ETO oncogene bypasses embryonic lethality and establishes a murine model of human t(8;21) acute myeloid leukemia. Cancer Cell 1, 63–74 (2002).
Article CAS PubMed Google Scholar
- Sinenko, S. A. et al. Genetic manipulation of AML1-ETO-induced expansion of hematopoietic precursors in a Drosophila model. Blood 116, 4612–4620 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Osman, D. et al. A Drosophila model identifies calpains as modulators of the human leukemogenic fusion protein AML1-ETO. Proc. Natl Acad. Sci. USA 106, 12043–12048 (2009). This paper used D. melanogaster to identify genes involved in leukaemogenesis.
Article CAS PubMed PubMed Central Google Scholar
- Wandler, A. M. & Guillemin, K. Transgenic expression of the Helicobacter pylori virulence factor CagA promotes apoptosis or tumorigenesis through JNK activation in Drosophila. PLoS Pathog. 866, e1002939 (2012).
Article CAS Google Scholar
- Ohlstein, B. & Spradling, A. The adult Drosophila posterior midgut is maintained by pluripotent stem cells. Nature 439, 470–474 (2006).
Article CAS PubMed Google Scholar
- Micchelli, C. A. & Perrimon, N. Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature 439, 475–479 (2006).
Article CAS PubMed Google Scholar
- Cordero, J., Vidal, M. & Sansom, O. APC as a master regulator of intestinal homeostasis and transformation: from flies to vertebrates. Cell Cycle 8, 2926–2931 (2009).
Article PubMed Google Scholar
- Cordero, J. B., Stefanatos, R. K., Scopelliti, A., Vidal, M. & Sansom, O. J. Inducible progenitor-derived Wingless regulates adult midgut regeneration in Drosophila. EMBO J. 31, 3901–3917 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Lee, W. C., Beebe, K., Sudmeier, L. & Micchelli, C. A. Adenomatous polyposis coli regulates Drosophila intestinal stem cell proliferation. Development 136, 2255–2264 (2009). References 88 and 89 describe the role of Wingless signalling in tumour suppression in the fly gut.
Article CAS PubMed Google Scholar
- Apidianakis, Y., Pitsouli, C., Perrimon, N. & Rahme, L. Synergy between bacterial infection and genetic predisposition in intestinal dysplasia. Proc. Natl Acad. Sci. USA 106, 20883–20888 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Jiang, H. & Edgar, B. A. Intestinal stem cell function in Drosophila and mice. Curr. Opin. Genet. Dev. 22, 354–360 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Jiang, H., Grenley, M. O., Bravo, M. J., Blumhagen, R. Z. & Edgar, B. A. EGFR/Ras/MAPK signaling mediates adult midgut epithelial homeostasis and regeneration in Drosophila. Cell Stem Cell 8, 84–95 (2011).
Article CAS PubMed Google Scholar
- Jiang, H. et al. Cytokine/Jak/Stat signaling mediates regeneration and homeostasis in the Drosophila midgut. Cell 137, 1343–1355 (2009).
Article PubMed PubMed Central Google Scholar
- Negrini, S., Gorgoulis, V. G. & Halazonetis, T. D. Genomic instability-an evolving hallmark of cancer. Nature Rev. Mol. Cell Biol. 11, 220–228 (2010).
Article CAS Google Scholar
- Holland, A. J. & Cleveland, D. W. Losing balance: the origin and impact of aneuploidy in cancer. EMBO Rep. 13, 501–514 (2012).
Article CAS PubMed PubMed Central Google Scholar
- McGranahan, N., Burrell, R. A., Endesfelder, D., Novelli, M. R. & Swanton, C. Cancer chromosomal instability: therapeutic and diagnostic challenges. EMBO Rep. 13, 528–538 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Pfau, S. J. & Amon, A. Chromosomal instability and aneuploidy in cancer: from yeast to man. EMBO Rep. 13, 515–527 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Raffa, G. D., Ciapponi, L., Cenci, G. & Gatti, M. Terminin: a protein complex that mediates epigenetic maintenance of Drosophila telomeres. Nucleus 2, 383–391 (2011).
Article PubMed Google Scholar
- Muller, H. J. An analysis of the process of structural change in chromosomes of Drosophila. J. Genet. 40, 1–66 (1940).
Article Google Scholar
- Titen, S. W. & Golic, K. G. Telomere loss provokes multiple pathways to apoptosis and produces genomic instability in Drosophila melanogaster. Genetics 180, 1821–1832 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Morciano, P. et al. A conserved role for the mitochondrial citrate transporter Sea/SLC25A1 in the maintenance of chromosome integrity. Hum. Mol. Genet. 18, 4180–4188 (2009).
Article CAS PubMed Google Scholar
- Fox, D. T., Gall, J. G. & Spradling, A. C. Error-prone polyploid mitosis during normal Drosophila development. Genes Dev. 24, 2294–2302 (2010).
Article CAS PubMed PubMed Central Google Scholar
- Anderhub, S. J., Kramer, A. & Maier, B. Centrosome amplification in tumorigenesis. Cancer Lett. 322, 8–17 (2012).
Article CAS PubMed Google Scholar
- Caussinus, E. & Gonzalez, C. Induction of tumor growth by altered stem-cell asymmetric division in Drosophila melanogaster. Nature Genet. 37, 1125–1129 (2005). This paper describes a causal link between failed asymmetric division and tumour growth.
Article CAS PubMed Google Scholar
- Basto, R. et al. Centrosome amplification can initiate tumorigenesis in flies. Cell 133, 1032–1042 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Ganem, N. J., Godinho, S. A. & Pellman, D. A mechanism linking extra centrosomes to chromosomal instability. Nature 460, 278–282 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Silkworth, W. T., Nardi, I. K., Scholl, L. M. & Cimini, D. Multipolar spindle pole coalescence is a major source of kinetochore mis-attachment and chromosome mis-segregation in cancer cells. PLoS ONE 466, e6564 (2009).
Article CAS Google Scholar
- Crasta, K. et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature 482, 53–58 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Castellanos, E., Dominguez, P. & Gonzalez, C. Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr. Biol. 18, 1209–1214 (2008). Together with reference 105, these papers demonstrated that centrosome dysfunction causes tumours in D. melanogaster larval brains.
Article CAS PubMed Google Scholar
- Kusano, K., Berres, M. E. & Engels, W. R. Evolution of the RECQ family of helicases: a Drosophila homolog, Dmblm, is similar to the human bloom syndrome gene. Genetics 151, 1027–1039 (1999).
CAS PubMed PubMed Central Google Scholar
- Garcia, A. M. et al. Loss of the bloom syndrome helicase increases DNA ligase 4-independent genome rearrangements and tumorigenesis in aging Drosophila. Genome Biol. 1266, R121 (2011). This paper showed a direct correlation between compromised DNA integrity and an increased rate of spontaneous tumours in D. melanogaster.
Article CAS Google Scholar
- Amor-Gueret, M. Bloom syndrome, genomic instability and cancer: the SOS-like hypothesis. Cancer Lett. 236, 1–12 (2006).
Article CAS PubMed Google Scholar
- Wu, M. et al. Imaging hematopoietic precursor division in real time. Cell Stem Cell 1, 541–554 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Westhoff, B. et al. Alterations of the Notch pathway in lung cancer. Proc. Natl Acad. Sci. USA 106, 22293–22298 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Cicalese, A. et al. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell 138, 1083–1095 (2009).
Article CAS PubMed Google Scholar
- Sugiarto, S. et al. Asymmetry-defective oligodendrocyte progenitors are glioma precursors. Cancer Cell 20, 328–340 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Goulas, S., Conder, R. & Knoblich, J. A. The par complex and integrins direct asymmetric cell division in adult intestinal stem cells. Cell Stem Cell 11, 529–540 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Egger, B., Chell, J. M. & Brand, A. H. Insights into neural stem cell biology from flies. Phil. Trans. R. Soc. B 363, 39–56 (2008).
Article CAS PubMed Google Scholar
- Knoblich, J. A. Mechanisms of asymmetric stem cell division. Cell 132, 583–597 (2008).
Article CAS PubMed Google Scholar
- Egger, B., Gold, K. S. & Brand, A. H. Regulating the balance between symmetric and asymmetric stem cell division in the developing brain. Fly 5, 237–241 (2011).
Article CAS PubMed Google Scholar
- Martin-Belmonte, F. & Perez-Moreno, M. Epithelial cell polarity, stem cells and cancer. Nature Rev. Cancer 12, 23–38 (2012).
Article CAS Google Scholar
- Chang, K. C., Wang, C. & Wang, H. Balancing self-renewal and differentiation by asymmetric division: insights from brain tumor suppressors in Drosophila neural stem cells. Bioessays 34, 301–310 (2012).
Article PubMed Google Scholar
- Januschke, J. & Gonzalez, C. Drosophila asymmetric division, polarity and cancer. Oncogene 27, 6994–7002 (2008).
Article CAS PubMed Google Scholar
- Wang, H. et al. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev. 20, 3453–3463 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Wang, H., Ouyang, Y., Somers, W. G., Chia, W. & Lu, B. Polo inhibits progenitor self-renewal and regulates Numb asymmetry by phosphorylating Pon. Nature 449, 96–100 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Lee, C. Y. et al. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev. 20, 3464–3474 (2006). References 124–126 demonstrated that the Aurora and POLO kinases act as tumour suppressors in the larval brain of D. melanogaster.
Article CAS PubMed PubMed Central Google Scholar
- Brachmann, S., Fritsch, C., Maira, S. M. & Garcia-Echeverria, C. PI3K and mTOR inhibitors: a new generation of targeted anticancer agents. Curr. Opin. Cell Biol. 21, 194–198 (2009).
Article CAS PubMed Google Scholar
- Willecke, M., Toggweiler, J. & Basler, K. Loss of PI3K blocks cell-cycle progression in a Drosophila tumor model. Oncogene 30, 4067–4074 (2011).
Article CAS PubMed Google Scholar
- Rossi, F. & Gonzalez, C. Synergism between altered cortical polarity and the PI3K/TOR pathway in the suppression of tumour growth. EMBO Rep. 13, 157–162 (2011).
Article PubMed Central CAS Google Scholar
- Martins, T., Maia, A. F., Steffensen, S. & Sunkel, C. E. Sgt1, a co-chaperone of Hsp90 stabilizes Polo and is required for centrosome organization. EMBO J. 28, 234–247 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Andersen, R. O., Turnbull, D. W., Johnson, E. A. & Doe, C. Q. Sgt1 acts via an LKB1/AMPK pathway to establish cortical polarity in larval neuroblasts. Dev. Biol. 363, 258–265 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Bonaccorsi, S. et al. The Drosophila Lkb1 kinase is required for spindle formation and asymmetric neuroblast division. Development 134, 2183–2193 (2007).
Article CAS PubMed Google Scholar
- Yamamoto, Y., Izumi, Y. & Matsuzaki, F. The GC kinase Fray and Mo25 regulate Drosophila asymmetric divisions. Biochem. Biophys. Res. Commun. 366, 212–218 (2008).
Article CAS PubMed Google Scholar
- Martin, S. G. & St Johnston, D. A role for Drosophila LKB1 in anterior-posterior axis formation and epithelial polarity. Nature 421, 379–384 (2003).
Article CAS PubMed Google Scholar
- Mirouse, V., Swick, L. L., Kazgan, N., St Johnston, D. & Brenman, J. E. LKB1 and AMPK maintain epithelial cell polarity under energetic stress. J. Cell Biol. 177, 387–392 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Richly, H., Aloia, L. & Di Croce, L. Roles of the Polycomb group proteins in stem cells and cancer. Cell Death Dis. 266, e204 (2011).
Article CAS Google Scholar
- Ferres-Marco, D. et al. Epigenetic silencers and Notch collaborate to promote malignant tumours by Rb silencing. Nature 439, 430–436 (2006).
Article CAS PubMed Google Scholar
- Martinez, A. M. et al. Polyhomeotic has a tumor suppressor activity mediated by repression of Notch signaling. Nature Genet. 41, 1076–1082 (2009).
Article CAS PubMed Google Scholar
- Feng, S., Thomas, S. & Wang, J. Diverse tumor pathology due to distinctive patterns of JAK/STAT pathway activation caused by different Drosophila polyhomeotic alleles. Genetics 190, 279–282 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Gonzalez, I., Simon, R. & Busturia, A. The Polyhomeotic protein induces hyperplastic tissue overgrowth through the activation of the JAK/STAT pathway. Cell Cycle 8, 4103–4111 (2009).
Article CAS PubMed Google Scholar
- Classen, A. K., Bunker, B. D., Harvey, K. F., Vaccari, T. & Bilder, D. A tumor suppressor activity of Drosophila Polycomb genes mediated by JAK-STAT signaling. Nature Genet. 41, 1150–1155 (2009).
Article CAS PubMed Google Scholar
- Simpson, A. J., Caballero, O. L., Jungbluth, A., Chen, Y. T. & Old, L. J. Cancer/testis antigens, gametogenesis and cancer. Nature Rev. Cancer 5, 615–625 (2005).
Article CAS Google Scholar
- Curran, S. P., Wu, X., Riedel, C. G. & Ruvkun, G. A soma-to-germline transformation in long-lived Caenorhabditis elegans mutants. Nature 459, 1079–1084 (2009).
Article CAS PubMed PubMed Central Google Scholar
- Geldmacher, A., Freier, A., Losch, F. O. & Walden, P. Therapeutic vaccination for cancer immunotherapy: antigen selection and clinical responses. Hum. Vaccin. 7, 115–119 (2011).
Article CAS PubMed Google Scholar
- Gateff, E., Loffler, T. & Wismar, J. A temperature-sensitive brain tumor suppressor mutation of Drosophila melanogaster: developmental studies and molecular localization of the gene. Mech. Dev. 41, 15–31 (1993).
Article CAS PubMed Google Scholar
- Janic, A., Mendizabal, L., Llamazares, S., Rossell, D. & Gonzalez, C. Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila. Science 330, 1824–1827 (2010). This paper describes a D. melanogaster model of somatic tumour growth that is driven by ectopic expression of germline genes.
Article CAS PubMed Google Scholar
- Meier, K. et al. LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes. PLoS Genet. 866, e1002676 (2012).
Article CAS Google Scholar
- Georlette, D. et al. Genomic profiling and expression studies reveal both positive and negative activities for the Drosophila Myb MuvB/dREAM complex in proliferating cells. Genes Dev. 21, 2880–2896 (2007).
Article CAS PubMed PubMed Central Google Scholar
- Munos, B. Lessons from 60 years of pharmaceutical innovation. Nature Rev. Drug Discov. 8, 959–968 (2009).
Article CAS Google Scholar
- Pandey, U. B. & Nichols, C. D. Human disease models in Drosophila melanogaster and the role of the fly in therapeutic drug discovery. Pharmacol. Rev. 63, 411–436 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Gladstone, M. & Su, T. T. Chemical genetics and drug screening in Drosophila cancer models. J. Genet. Genom. 38, 497–504 (2011).
Article CAS Google Scholar
- Kim, B. H. et al. A small-molecule compound identified through a cell-based screening inhibits JAK/STAT pathway signaling in human cancer cells. Mol. Cancer Ther. 7, 2672–2680 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Kim, B. H. et al. MS-1020 is a novel small molecule that selectively inhibits JAK3 activity. Br. J. Haematol. 148, 132–143 (2010).
Article CAS PubMed Google Scholar
- Kim, B. H. et al. Benzoxathiol derivative BOT-4-one suppresses L540 lymphoma cell survival and proliferation via inhibition of JAK3/STAT3 signaling. Exp. Mol. Med. 43, 313–321 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Gonsalves, F. C. et al. An RNAi-based chemical genetic screen identifies three small-molecule inhibitors of the Wnt/wingless signaling pathway. Proc. Natl Acad. Sci. USA 108, 5954–5963 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Read, R. D. et al. A Drosophila model of multiple endocrine neoplasia type 2. Genetics 171, 1057–1081 (2005).
Article CAS PubMed PubMed Central Google Scholar
- Vidal, M., Wells, S., Ryan, A. & Cagan, R. ZD6474 suppresses oncogenic RET isoforms in a Drosophila model for type 2 multiple endocrine neoplasia syndromes and papillary thyroid carcinoma. Cancer Res. 65, 3538–3541 (2005).
Article CAS PubMed Google Scholar
- Das, T. & Cagan, R. Drosophila as a novel therapeutic discovery tool for thyroid cancer. Thyroid 20, 689–695 (2010).
Article CAS PubMed Google Scholar
- Dar, A. C., Das, T. K., Shokat, K. M. & Cagan, R. L. Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature 486, 80–84 (2012). This paper used a D. melanogaster tumour model to optimize anticancer drugs.
Article CAS PubMed PubMed Central Google Scholar
- Jaklevic, B. et al. Contribution of growth and cell cycle checkpoints to radiation survival in Drosophila. Genetics 174, 1963–1972 (2006).
Article CAS PubMed PubMed Central Google Scholar
- Edwards, A. et al. Combinatorial effect of maytansinol and radiation in Drosophila and human cancer cells. Dis. Model. Mech. 4, 496–503 (2011).
Article CAS PubMed PubMed Central Google Scholar
- Jolad, S. D. et al. Bouvardin and deoxybouvardin, antitumor cyclic hexapeptides from Bouvardia ternifolia (Rubiaceae). J. Am. Chem. Soc. 99, 8040–8044 (1977).
Article CAS PubMed Google Scholar
- Gladstone, M. et al. A translation inhibitor identified in a Drosophila screen enhances the effect of ionizing radiation and taxol in mammalian models of cancer. Dis. Model. Mech. 5, 342–350 (2012).
Article CAS PubMed PubMed Central Google Scholar
- Willoughby, L. F. et al. An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis. Model. Mech. 20 Sep 2012 (doi:10.1242/dmm.009985). References 163 and 164 describe pioneering in vivo chemical screens for cancer treatment drugs using D. melanogaster.
- Hardy, P. A. & Zacharias, H. Reappraisal of the Hansemann-Boveri hypothesis on the origin of tumors. Cell Biol. Int. 29, 983–992 (2005).
Article PubMed Google Scholar
- Dickson, B. & Hafen, E. in The Development of Drosophila Melanogaster ( eds Bate, M. & Martinez-Arias, A. ) 1327–1362 (Cold Spring Harbor Laboratory Press, 1993).
- Morris, E. J. et al. E2F1 represses β-catenin transcription and is antagonized by both pRB and CDK8. Nature 455, 552–556 (2008).
Article CAS PubMed PubMed Central Google Scholar
- Bello, B., Reichert, H. & Hirth, F. The brain tumor gene negatively regulates neural progenitor cell proliferation in the larval central brain of Drosophila. Development 133, 2639–2648 (2006).
Article CAS PubMed Google Scholar