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The flower code and cancer development

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  • Molecular and Cellular Biology of Cancer
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Abstract

It has been postulated that the preliminary steps of cancer known as “cancerization field” could be mediated by a competitive mechanism among mutated and wild-type cells. Cell competition is a process of selection among populations of cells with different fitness: the best adapted cells (winners) survive and proliferate in the tissue at the expense of the less well adapted cells (losers), and these loser cells are eliminated from the tissue by apoptosis. However, the molecular mechanisms mediating this process and the genes involved are still unknown. A mechanism of cell-to-cell communication during cell competition known as the “flower code” has been recently proposed to distinguish loser from winner cells: fweubi isoform is expressed ubiquitously in the imaginal disc while fweLose isoforms are expressed specifically during cell competition in the cells to be eliminated. Cell competition has been postulated to have implications in development, tissue homeostasis, regeneration and tumour development; the process of cell competition does not affect the total cell number and organ morphology is maintained because winner cells compensate for the loss. A role of cell competition as the mechanism occurring during initial stages of tumour formation is currently under study.

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References

  1. Morata G, Ripoll P (1975) Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev Biol 42:211–221

    Article  CAS  PubMed  Google Scholar 

  2. Moreno E, Basler K, Morata G (2002) Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416:755–759

    Article  CAS  PubMed  Google Scholar 

  3. Moreno E, Basler K (2004) Dmyc transforms cells into super-competitors. Cell 117:117–129

    Article  CAS  PubMed  Google Scholar 

  4. Johnston LA (2009) Competitive interactions between cells: death, growth, and geography. Science 324:1679–1682

    Article  CAS  PubMed  Google Scholar 

  5. Moreno E (2008) Is cell competition relevant to cancer? Nat Rev Cancer 8:141–147

    Article  CAS  PubMed  Google Scholar 

  6. Rhiner C, Moreno E (2009) Super competition as a possible mechanism to pioneer precancerous fields. Carcinogenesis 30:723–728

    Article  CAS  PubMed  Google Scholar 

  7. Rhiner C, López-Gay JM, Soldini D et al (2010) Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev Cell 18:1–14

    Article  Google Scholar 

  8. Grzeschik NA, Amin N, Secombe J et al (2007) Abnormalities in cell proliferation and apicobasal cell polarity are separable in Drosophila lgl mutant clones in the developing eye. Dev Biol 311:106–123

    Article  CAS  PubMed  Google Scholar 

  9. Bilder D, Li M, Perrimon N (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289:113–116

    Article  CAS  PubMed  Google Scholar 

  10. Humbert P, Russell S, Richardson H (2003) Dlg, scribble and lgl in cell polarity, cell proliferation and cancer. Bioessays 25:542–553

    Article  CAS  PubMed  Google Scholar 

  11. Woods DF, Bryants PJ (1991) The disc-large tumor suppressor gene of Drosophila encodes a guanylate kinase homolog localized at septate junctions. Cell 66:451–464

    Article  CAS  PubMed  Google Scholar 

  12. Agrawal N, Kango M, Mishra A, Sinha P (1995) Neoplastic transformation and aberrant cell-cell interactions in genetic mosaics of lethal(2)giant larvae (lgl), a tumor suppressor gene of Drosophila. Dev Biol 172:218–229

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  14. Hariharan IK, Bilder D (2006) Regulation of imaginal disc growth by tumor-suppressor genes in Drosophila. Annu Rev Genet 40:335–361

    Article  CAS  PubMed  Google Scholar 

  15. de la Cova C, Abril M, Bellosta P et al (2004) Drosophila myc regulates organ size by inducing cell competition. Cell 117:107–116

    Article  PubMed  Google Scholar 

  16. Merlo LM, Pepper JW, Reid BJ, Maley CC (2006) Cancer as an evolutionary and ecological process. Nat Rev Cancer 6:924–935

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  19. 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 

  20. Boutros M, Ahringer J (2008) The art and design of genetic screens: Rna interference. Nat Rev Genet 9:554–566

    Article  CAS  PubMed  Google Scholar 

  21. Reiter LT, Potocki L, Chien S et al (2001) A systematic analysis of human disease-associated gene sequences in Drosophila melanogaster. Genome Res 11:1114–1125

    Article  CAS  PubMed  Google Scholar 

  22. Vaccari T, Bilder D (2005) The Drosophila tumor suppressor vps25 prevents nonautonomous over-proliferation by regulating notch trafficking. Dev Cell 9:687–698

    Article  CAS  PubMed  Google Scholar 

  23. Vidal M, Cagan RL (2006) Drosophila models for cancer research. Curr Opin Genet Dev 16:10–16

    Article  CAS  PubMed  Google Scholar 

  24. Humbert PO, Grzeschik NA, Brumby AM et al (2008) Control of tumourigenesis by the scribble/dlg/lgl polarity module. Oncogene 27:6888–6907

    Article  CAS  PubMed  Google Scholar 

  25. Zhao B, Li L, Lei Q, Guan KL (2010) The hippoyap pathway in organ size control and tumorigenesis: an updated version. Genes Dev 24:862–874

    Article  CAS  PubMed  Google Scholar 

  26. Thompson BJ, Mathieu J, Sung HH et al (2005) Tumor suppressor properties of the escrt-ii complex component vps25 in Drosophila. Dev Cell 9:711–720

    Article  CAS  PubMed  Google Scholar 

  27. Read RD, Cavenee WK, Furnari FB, Thomas JB (2009) A Drosophila model for egfr-ras and pi3k-dependent human glioma. PLoS Genet 5(2)

  28. Zecca M, Struhl G (2010) A feed-forward circuit linking wingless, fat-dachsous signaling, and the warts-hippo pathway to Drosophila wing growth. PLoS Biol 8:e1000386

    Article  PubMed  Google Scholar 

  29. Marusyk A, Porter CC, Zaberezhnyy V, DeGregori J (2010) Irradiation selects for p53-deficient hematopoietic progenitors. PLoS Biol 8(3)

  30. Bondar T, Medzhitov R (2010) P53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 6:309–322

    Article  CAS  PubMed  Google Scholar 

  31. Rhiner C, Diaz B, Portela M et al (2009) Persistent competition among stem cells and their daughters in the Drosophila ovary germline niche. Development 136:995–1006

    Article  CAS  PubMed  Google Scholar 

  32. Klein CA (2008) Cancer. The metastasis cascade. Science 321:1785–1787

    CAS  Google Scholar 

  33. Tyler DM, Li W, Zhuo N et al (2007) Genes affecting cell competition in Drosophila. Genetics 175:643–657

    Article  CAS  PubMed  Google Scholar 

  34. Senoo-Matsuda N, Johnston LA (2007) Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila myc. Proc Natl Acad Sci U S A 104:18543–18548

    Article  CAS  PubMed  Google Scholar 

  35. Igaki T, Kanda H, Yamamoto-Goto Y et al (2002) Eiger, a TNF superfamily ligand that triggers the Drosophila JNK pathway. EMBO J 21:3009–3018

    Article  CAS  PubMed  Google Scholar 

  36. Moreno E, Yan M, Basler K (2002) Evolution of TNF signaling mechanisms: JNK-dependent apoptosis triggered by eiger, the Drosophila homolog of the TNF superfamily. Curr Biol 12:1263–1268

    Article  CAS  PubMed  Google Scholar 

  37. Cordero JB, Macagno JP, Stefanatos RK et al (2010) Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev Cell 18:999–1011

    Article  CAS  PubMed  Google Scholar 

  38. Igaki T, Pagliarini RA, Xu T (2006) Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol 16:1139–1146

    Article  CAS  PubMed  Google Scholar 

  39. Igaki T, Pastor-Pareja JC, Aonuma H et al (2009) Intrinsic tumor suppression and epithelial maintenance by endocytic activation of eiger/TNF signaling in Drosophila. Dev Cell 16:458–465

    Article  CAS  PubMed  Google Scholar 

  40. Yao CK, Lin YQ, Ly CV et al (2009) A synaptic vesicle-associated ca2+ channel promotes endocytosis and couples exocytosis to endocytosis. Cell 138:947–960

    Article  CAS  PubMed  Google Scholar 

  41. Hassig R (1988) Aztec warfare: imperial expansion and political control (Civilization of the American Indian series 188). University of Oklahoma Press. Oklahoma, USA

    Google Scholar 

  42. Moreno E (2010) A war-prone tribe migrated out of Africa to populate the world. Available from Nature Precedings (http://hdl.handle.net/10101/npre.2010.4303.1)

  43. Portela M, Casas-Tinto S, Rhiner C et al (2010) Drosophila SPARC is a self-protective signal expressed by loser cells during cell competition. Dev Cell 19:562–573

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Eduardo Moreno.

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Casas-Tinto, S., Torres, M. & Moreno, E. The flower code and cancer development. Clin Transl Oncol 13, 5–9 (2011). https://doi.org/10.1007/s12094-011-0610-4

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  • DOI: https://doi.org/10.1007/s12094-011-0610-4

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