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Mechanisms and mechanics of cell competition in epithelia

Nature Reviews Molecular Cell Biology volume 14, pages 581–591 (2013)Cite this article

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Key Points

  • Cells with reduced protein synthesis capacity are eliminated by apoptosis if they are in contact with normal cells but are viable on their own. Conversely, normal cells are eliminated by the presence of abnormally fast-growing cells. This phenomenon, called cell competition, could have evolved as a mechanism to eliminate slow-growing, dysfunctional or aneuploid cells.

  • Cell competition has now been observed in various mosaic tissues. For example, cells deficient in basolateral determinants are eliminated when surrounded by normal cells but not in their own company. It is not known whether the same cell biological mechanism underlies cell competition caused by polarity mismatch and a growth differential.

  • How cells within a population compare their growth rates and how a steep difference leads to the elimination of loser cells are two questions under intense investigation. So far, alternative splicing of the multipass transmembrane protein Flower is the only molecular marker of loser cells (outcompeted cells).

  • Although it is generally assumed that loser cells are killed by a signal emanating from winner cells (faster-growing cells), it has also been suggested that apoptosis could be an indirect consequence of either engulfment by winner cells or delamination caused by differential growth.

  • Recent work has shown that, in Madin–Darby canine kidney (MDCK) cell culture and in the prospective notum of Drosophila melanogaster, tissue crowding leads to the random expulsion of cells from the epithelium and their subsequent apoptosis.

  • Using an established vertex model of epithelial mechanics, the stresses and strains caused by inhomogeneous growth can be predicted. A group of fast-growing cells could cause planar elongation of the surrounding slower-growing cells. This could be the trigger for subsequent delamination and cell elimination. Therefore, strain caused by mechanical stress could contribute to cell competition.

Abstract

When fast-growing cells are confronted with slow-growing cells in a mosaic tissue, the slow-growing cells are often progressively eliminated by apoptosis through a process known as cell competition. The underlying signalling pathways remain unknown, but recent findings have shown that cell crowding within an epithelium leads to the eviction of cells from the epithelial sheet. This suggests that mechanical forces could contribute to cell elimination during cell competition.

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Figure 1: Topologies of cell competition.
Figure 2: Triggers of cell competition.
Figure 3: Apoptosis in Minute+/− cells occurs in the vicinity of wild-type cells in Drosophila melanogaster imaginal discs.
Figure 4: Direct and indirect triggers of apoptosis.
Figure 5: Predicted stresses and strains in an around a fast-growing clone of cells.

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References

  1. Plagge, A., Kelsey, G. & Allen, N. D. in Mouse genetics and transgenics, a practical apporach (eds Jackson, I. J. & Abbott, C. M.) (Oxford Univ. Press, 2000).

    Google Scholar 

  2. Oliver, E. R., Saunders, T. L., Tarlé, S. A. & Glaser, T. Ribosomal protein L24 defect in belly spot and tail (Bst), a mouse Minute. Development 131, 3907–3920 (2004). Provides the first evidence for cell competition in mammals.

    Article  CAS  PubMed  Google Scholar 

  3. Oertel, M., Menthena, A., Dabeva, M. D. & Shafritz, D. A. Cell competition leads to a high level of normal liver reconstitution by transplanted fetal liver stem/progenitor cells. Gastroenterology 130, 507–520 (2006).

    Article  PubMed  Google Scholar 

  4. Bondar, T. & Medzhitov, R. p53-mediated hematopoietic stem and progenitor cell competition. Cell Stem Cell 6, 309–322 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Alexander, D. B. et al. Normal cells control the growth of neighboring transformed cells independent of gap junctional communication and SRC activity. Cancer Res. 64, 1347–1358 (2004).

    Article  CAS  PubMed  Google Scholar 

  6. Bignami, M., Rosa, S., La Rocca, S. A., Falcone, G. & Tatò, F. Differential influence of adjacent normal cells on the proliferation of mammalian cells transformed by the viral oncogenes myc, ras and src. Oncogene 2, 509–514 (1988).

    CAS  PubMed  Google Scholar 

  7. Borek, C. & Sachs, L. The difference in contact inhibition of cell replication between normal cells and cells transformed by different carcinogens. Proc. Natl Acad. Sci. USA 56, 1705–1711 (1966).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. de Beco, S., Ziosi, M. & Johnston, L. A. New frontiers in cell competition. Dev. Dynam. 241, 831–841 (2012).

    Article  Google Scholar 

  9. Vivarelli, S., Wagstaff, L. & Piddini, E. Cell wars: regulation of cell survival and proliferation by cell competition. Essays Biochem. 53, 69–82 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  11. Baker, N. E. & Li, W. Cell competition and its possible relation to cancer. Cancer Res. 68, 5505–5507 (2008).

    Article  CAS  PubMed  Google Scholar 

  12. Hogan, C., Kajita, M., Lawrenson, K. & Fujita, Y. Interactions between normal and transformed epithelial cells: their contributions to tumourigenesis. Int. J. Biochem. Cell Biol. 43, 496–503 (2011).

    Article  CAS  PubMed  Google Scholar 

  13. Morata, G. & Ripoll, P. Minutes: mutants of Drosophila autonomously affecting cell division rate. Dev. Biol. 42, 211–221 (1975). The first description of cell competition.

    Article  CAS  PubMed  Google Scholar 

  14. Moreno, E., Basler, K. & Morata, G. Cells compete for decapentaplegic survival factor to prevent apoptosis in Drosophila wing development. Nature 416, 755–759 (2002). Shows that cell death is a landmark of cell competition.

    Article  CAS  PubMed  Google Scholar 

  15. Tamori, Y. & Deng, W.-M. Cell competition and its implications for development and cancer. J. Genet. Genom. 38, 483–495 (2011).

    Article  CAS  Google Scholar 

  16. Simpson, P. & Morata, G. Differential mitotic rates and patterns of growth in compartments in the Drosophila wing. Dev. Biol. 85, 299–308 (1981).

    Article  CAS  PubMed  Google Scholar 

  17. Ferrus, A. Parameters of mitotic recombination in minute mutants of Drosophila melanogaster. Genetics 79, 589–599 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Tyler, D. M. & Baker, N. E. Expanded and fat regulate growth and differentiation in the Drosophila eye through multiple signaling pathways. Dev. Biol. 305, 187–201 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Martín, F. A., Herrera, S. C. & Morata, G. Cell competition, growth and size control in the Drosophila wing imaginal disc. Development 136, 3747–3756 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Li, W. & Baker, N. E. Engulfment is required for cell competition. Cell 129, 1215–1225 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. Rhiner, C. et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev. Cell 18, 985–998 (2010).

    Article  CAS  PubMed  Google Scholar 

  23. 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 

  24. Xu, T. & Rubin, G. M. The effort to make mosaic analysis a household tool. Development 139, 4501–4503 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. de la Cova, C., Abril, M., Bellosta, P., Gallant, P. & Johnston, L. A. Drosophila myc regulates organ size by inducing cell competition. Cell 117, 107–116 (2004).

    Article  CAS  PubMed  Google Scholar 

  26. Moreno, E. & Basler, K. dMyc transforms cells into super-competitors. Cell 117, 117–129 (2004). Demonstrates, together with reference 25, that Myc is a cell competition factor and discovers super-competition.

    Article  CAS  PubMed  Google Scholar 

  27. Garcia-Bellido, A., Ripoll, P. & Morata, G. Developmental compartmentalisation of the wing disk of Drosophila. Nature: New Biol. 245, 251–253 (1973).

    Article  CAS  Google Scholar 

  28. Garcia-Bellido, A., Ripoll, P. & Morata, G. Developmental compartmentalization in the dorsal mesothoracic disc of Drosophila. Dev. Biol. 48, 132–147 (1976).

    Article  CAS  PubMed  Google Scholar 

  29. Marygold, S. The ribosomal protein genes and Minute loci of Drosophila melanogaster. 8, R216 (2007).

  30. Shraiman, B. I. Mechanical feedback as a possible regulator of tissue growth. Proc. Natl Acad. Sci. USA 102, 3318–3323 (2005). Suggests for the first time, that mechanics could influence tissue growth and cell competition.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moreno, E. Is cell competition relevant to cancer? Nature Rev. Cancer 8, 141–147 (2008).

    Article  CAS  Google Scholar 

  32. Baker, N. E. Cell competition. Curr. Biol. 21, R11–R15 (2011).

    Article  CAS  PubMed  Google Scholar 

  33. Lambertsson, A. The minute genes in Drosophila and their molecular functions. Adv. Genet. 38, 69–134 (1998).

    Article  CAS  PubMed  Google Scholar 

  34. 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 

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

    Article  CAS  PubMed  Google Scholar 

  36. Igaki, T., Pastor-Pareja, J. C., Aonuma, H., Miura, M. & Xu, T. Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev. Cell 16, 458–465 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Pagliarini, R. A. & Xu, T. A genetic screen in Drosophila for metastatic behavior. Science 302, 1227–1231 (2003).

    Article  CAS  PubMed  Google Scholar 

  38. 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 

  39. 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 

  40. Tamori, Y. & Deng, W.-M. Tissue repair through cell competition and compensatory cellular hypertrophy in postmitotic epithelia. Dev. Cell 25, 350–363 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Huang, J., Wu, S., Barrera, J., Matthews, K. & Pan, D. The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila homolog of YAP. Cell 122, 421–434 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. Pan, D. The Hippo signaling pathway in development and cancer. Dev. Cell 19, 491–505 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Halder, G. & Johnson, R. L. Hippo signaling: growth control and beyond. Development 138, 9–22 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Tyler, D. M., Li, W., Zhuo, N., Pellock, B. & Baker, N. E. Genes affecting cell competition in Drosophila. Genetics 175, 643–657 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Menéndez, J., Pérez-Garijo, A., Calleja, M. & Morata, G. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. Proc. Natl Acad. Sci. 107, 14651–14656 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  46. 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. 109, 484–489 (2012).

    Article  PubMed  Google Scholar 

  47. Ziosi, M. et al. dMyc functions downstream of Yorkie to promote the supercompetitive behavior of hippo pathway mutant cells. PLoS Genet. 6, e100114 (2010).

    Article  CAS  Google Scholar 

  48. Tapon, N. et al. Salvador promotes both cell cycle exit and apoptosis in Drosophila and is mutated in human cancer cell lines. Cell 110, 467–478 (2002).

    Article  CAS  PubMed  Google Scholar 

  49. Udan, R. S., Kango-Singh, M., Nolo, R., Tao, C. & Halder, G. Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nature Cell Biol. 5, 914–920 (2003).

    Article  CAS  PubMed  Google Scholar 

  50. Lee, K.-P. et al. The Hippo–Salvador pathway restrains hepatic oval cell proliferation, liver size, and liver tumorigenesis. Proc. Natl Acad. Sci. 107, 8248–8253 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Song, H. et al. Mammalian Mst1 and Mst2 kinases play essential roles in organ size control and tumor suppression. Proc. Natl Acad. Sci. 107, 1431–1436 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  52. Xu, T., Wang, W., Zhang, S., Stewart, R. A. & Yu, W. Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development 121, 1053–1063 (1995).

    CAS  PubMed  Google Scholar 

  53. Cho, E. et al. Delineation of a Fat tumor suppressor pathway. Nature Genet. 38, 1142–1150 (2006).

    Article  CAS  PubMed  Google Scholar 

  54. Bennett, F. C. & Harvey, K. F. Fat cadherin modulates organ size in Drosophila via the Salvador/Warts/Hippo signaling pathway. Curr. Biol. 16, 2101–2110 (2006).

    Article  CAS  PubMed  Google Scholar 

  55. Willecke, M. et al. The Fat cadherin acts through the Hippo tumor-suppressor pathway to regulate tissue size. Curr. Biol. 16, 2090–2100 (2006).

    Article  CAS  PubMed  Google Scholar 

  56. Justice, R. W., Zilian, O., Woods, D. F., Noll, M. & Bryant, P. J. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation. Genes Dev. 9, 534–546 (1995).

    Article  CAS  PubMed  Google Scholar 

  57. Neto-Silva, R. M., de Beco, S. & Johnston, L. A. Evidence for a growth-stabilizing regulatory feedback mechanism between Myc and Yorkie, the Drosophila homolog of Yap. Dev. Cell 19, 507–520 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Böhni, R. et al. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97, 865–875 (1999).

    Article  PubMed  Google Scholar 

  59. Potter, C. J., Tasic, B., Russler, E. V., Liang, L. & Luo, L. The Q system: a repressible binary system for transgene expression, lineage tracing, and mosaic analysis. Cell 141, 536–548 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Froldi, F. et al. The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol. 8, 33 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 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 

  62. Tamori, Y. et al. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 8, e1000422 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Humbert, P. O. et al. Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module. Oncogene 27, 6888–6907 (2008).

    Article  CAS  PubMed  Google Scholar 

  64. Gateff, E. Malignant neoplasms of genetic origin in Drosophila melanogaster. Science 200, 1448–1459 (1978).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  66. Garelli, A., Gontijo, A. M., Miguela, V., Caparros, E. & Dominguez, M. Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation. Science 336, 579–582 (2012).

    Article  CAS  PubMed  Google Scholar 

  67. Colombani, J., Andersen, D. S. & Léopold, P. Secreted peptide Dilp8 coordinates Drosophila tissue growth with developmental timing. Science 336, 582–585 (2012).

    Article  CAS  PubMed  Google Scholar 

  68. Norman, M. et al. Loss of Scribble causes cell competition in mammalian cells. J. Cell Sci. 125, 59–66 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Prober, D. A. & Edgar, B. A. Ras1 promotes cellular growth in the Drosophila wing. Cell 100, 435–446 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Zhan, L. et al. Deregulation of Scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma. Cell 135, 865–878 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Martín, F. A., Pérez-Garijo, A. & Morata, G. Apoptosis in Drosophila: compensatory proliferation and undead cells. Int. J. Dev. Biol. 53, 1341–1347 (2009).

    Article  PubMed  Google Scholar 

  72. Rosenblatt, J., Raff, M. C. & Cramer, L. P. An epithelial cell destined for apoptosis signals its neighbors to extrude it by an actin- and myosin-dependent mechanism. Curr. Biol. 11, 1847–1857 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Senoo-Matsuda, N. & Johnston, L. A. Soluble factors mediate competitive and cooperative interactions between cells expressing different levels of Drosophila Myc. Proc. Natl Acad. Sci. 104, 18543–18548 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Petrova, E., López-Gay, J. M., Rhiner, C. & Moreno, E. Flower-deficient mice have reduced susceptibility to skin papilloma formation. Dis. Models Mech. 5, 553–561 (2012).

    Article  CAS  Google Scholar 

  75. Ryoo, H. D., Domingos, P. M., Kang, M.-J. & Steller, H. Unfolded protein response in a Drosophila model for retinal degeneration. EMBO J. 26, 242–252 (2007).

    Article  CAS  PubMed  Google Scholar 

  76. Ohsawa, S. et al. Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev. Cell 20, 315–328 (2011).

    Article  CAS  PubMed  Google Scholar 

  77. Marinari, E. et al. Live-cell delamination counterbalances epithelial growth to limit tissue overcrowding. Nature 484, 542–545 (2012). Shows that cell crowding leads to live cell delamination in the D. melanogaster notum.

    Article  CAS  PubMed  Google Scholar 

  78. Eisenhoffer, G. T. et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484, 546–549 (2012). Demonstrates that cell crowding leads to live cell extrusion in MDCK epithelia.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Gu, Y., Forostyan, T., Sabbadini, R. & Rosenblatt, J. Epithelial cell extrusion requires the sphingosine-1-phosphate receptor 2 pathway. J. Cell Biol. 193, 667–676 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Bonnet, I. et al. Mechanical state, material properties and continuous description of an epithelial tissue. J. R. Soc., Interface 9, 2614–2623 (2012).

    Article  Google Scholar 

  82. Farhadifar, R., Röper, J.-C., Aigouy, B., Eaton, S. & Jülicher, F. The influence of cell mechanics, cell–cell interactions, and proliferation on epithelial packing. Curr. Biol. 17, 2095–2104 (2007). First biologist-friendly vertex model of epithelia.

    Article  CAS  PubMed  Google Scholar 

  83. Ranft, J. et al. Fluidization of tissues by cell division and apoptosis. Proc. Natl Acad. Sci. 107, 20863–20868 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  84. Landsberg, K. P. et al. Increased cell bond tension governs cell sorting at the Drosophila anteroposterior compartment boundary. Curr. Biol. 19, 1950–1955 (2009).

    Article  CAS  PubMed  Google Scholar 

  85. Levy, D. L. & Heald, R. Mechanisms of intracellular scaling. Annu. Rev. Cell Dev. Biol. 28, 113–135 (2012).

    Article  CAS  PubMed  Google Scholar 

  86. Teleman, A. A. Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem. J. 425, 13–26 (2010).

    Article  CAS  Google Scholar 

  87. Hannezo, E., Prost, J. & Joanny, J.-F. Instabilities of monolayered epithelia: shape and structure of villi and crypts. Phys. Rev. Lett. 107, 078104 (2011).

    Article  CAS  PubMed  Google Scholar 

  88. Mao, Y. et al. Planar polarization of the atypical myosin Dachs orients cell divisions in Drosophila. Genes Dev. 25, 131–136 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Aegerter-Wilmsen, T. et al. Exploring the effects of mechanical feedback on epithelial topology. Development 137, 499–506 (2010).

    Article  CAS  PubMed  Google Scholar 

  90. Vogel, V. & Sheetz, M. Local force and geometry sensing regulate cell functions. Nature Rev. Mol. Cell Biol. 7, 265–275 (2006).

    Article  CAS  Google Scholar 

  91. Rauzi, M., Lenne, P.-F. & Lecuit, T. Planar polarized actomyosin contractile flows control epithelial junction remodelling. Nature 468, 1110–1114 (2010).

    Article  CAS  PubMed  Google Scholar 

  92. Aigouy, B. et al. Cell flow reorients the axis of planar polarity in the wing epithelium of Drosophila. Cell 142, 773–786 (2010).

    Article  CAS  PubMed  Google Scholar 

  93. Ishihara, S. & Sugimura, K. Bayesian inference of force dynamics during morphogenesis. J. Theor. Biol. 313, 201–211 (2012).

    Article  PubMed  Google Scholar 

  94. Grashoff, C. et al. Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics. Nature 466, 263–266 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Claveria et al. Myc-driven endogenous cell competition in the early mammalian embryo. Nature http://dx.doi.org/10.1038/nature12389 (2013).

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Acknowledgements

The authors thank K. Rizzoti and R. Lovell-Badge for discussions about mouse mosaics. J.-P.V. is supported by the Medical Research Council (MRC) and the European Research Council (ERC) (WNTEXPORT),L.A.B.-L. by the Wellcome Trust (082694/z/07/z) and A.G.F. by the Engineering and Physical Sciences Research Council (EPSRC) (EP/I017909/1) and Microsoft Research Cambridge.

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  1. Medical Research Council (MRC) National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Jean-Paul Vincent & L. ALberto Baena-Lopez

  2. Centre for Mathematical Biology, Mathematical Institute, 24–29 St Giles', Oxford, OX1 3LB, UK

    Alexander G. Fletcher

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FURTHER INFORMATION

CancerStats

FlyBase

PowerPoint slides

Glossary

Genetic mosaics

Tissues comprised of genetically distinct cells. In Drosophila melanogaster, these are typically generated by inducing mitotic recombination in a heterozygous background, thus creating twin clones, one being homozygous wild type and the other homozygous mutant at a given locus.

Blastocysts

Early mammalian embryos composed of about 100 cells. Embryonic stem cells are injected into blastocysts to generate chimaeras before implantation into a surrogate mother.

Chimaeras

Embryos comprising cells of two distinct genotypes. They are usually generated by cell transplantation.

Apoptosis

One of the main processes leading to cell death. It involves the activation of a proteolytic cascade comprising initiator and executioner caspases.

Aneuploid cells

Cells that have lost or gained entire chromosomes or large chromosomal fragments as a consequence of chromosome rearrangements.

Myc

A proto-oncoprotein that controls ribosome biosynthesis, translational activity and other essential cellular activities.

Contact inhibition

A phenomenon whereby cells stop growing as their density increases.

Imaginal discs

Epithelial pouches that grow inside insect larvae and give rise to most adult structures during metamorphosis. They are extensively used to study pattern formation and growth control.

Apical–basal determinants

Proteins that ensure apical–basal polarity. Apical determinants such as atypical protein kinase A and basolateral determinants such as Scribble or Lethal giant larvae typically oppose each other's activity thus ensuring the partitioning of distinct domains.

Madin–Darby canine kidney cells

(MDCK cells). The best-characterized epithelial cell line.

Neoplastic overgrowth

Overgrowth that is accompanied by loss of polarity and general disorganisation of the tissue.

Hyperplastic overgrowth

Overgrowth that maintains cell polarity and tissue integrity. It is often accompanied by tissue folds.

Caspase

A class of proteases that initiate or execute apoptosis.

JUN N-terminal kinase

(JNK). The key mediator of a kinase cascade that is often activated by stress. Depending on the context, it can trigger cell migration or apoptosis.

hid

A gene encoding one of the five pro-apoptotic proteins in Drosophila melanogaster. It inhibits the activity of DIAP1 (D. melanogaster inhibitor of apoptosis 1), which itself inhibits caspases.

Epithelial-to-mesenchymal transition

(EMT). A process whereby epithelial cells lose their epithelial characteristics (for example, polarity), detach from the epithelium and become migratory.

PTEN

A negative regulator of insulin signalling. Loss of PTEN is associated with numerous cancers.

Tuberous sclerosis complex 1

(TSC1). A tumour suppressor that negatively regulates insulin signalling.

PI3K

A key mediator of insulin signalling. Upon activation of the insulin receptor, it converts phosphatidylinositol-4,5-bisphosphate to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3), an activity that is antagonized by PTEN. PtdIns(3,4,5)P3 activates AKT, which in turn triggers further downstream events.

Adherens junctions

Molecular complex that mediates cell–cell adhesion in epithelia. They are typically organized in belts that surround every cell near the apical side.

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Vincent, JP., Fletcher, A. & Baena-Lopez, L. Mechanisms and mechanics of cell competition in epithelia. Nat Rev Mol Cell Biol 14, 581–591 (2013). https://doi.org/10.1038/nrm3639

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