Cell Competition


Cell competition is a conserved mechanism by which unfit cells are outcompeted by fitter neighbours. This quality control mechanism allows the maintenance and propagation of fitter cells, by potentiating the elimination of unfit cells from tissues. Cell competition plays a central role during embryogenesis and in adulthood, contributing to proper development and preservation of tissues homeostasis. The absence of fitness control impacts organ function, which ultimately results in shorten lifespan and disease development. In fact, impairment of cell competition or the appropriation of this process by pre‐malignant cells can allow the expansion of potentially dangerous cells leading to tumorigenesis. Different molecular mechanisms and strategies have been described to be required for the elimination of unfit cells depending on the tissue context and genetics.

Key Concepts

  • Cell competition actively takes place since embryonic stages, throughout development and in the adult.
  • Cell competition is a conserved mechanism in multicellular animals.
  • When in the presence of fitter cells, unfit cells are eliminated from tissues by cell competition.
  • The context and genes involved determine the mechanism by which loser cells are eliminated.
  • Selection of fit cells to be maintained in tissues promote homeostasis and improves lifespan.
  • Accumulation of viable but less fit cells is detrimental for the organism.
  • Pre‐malignant cells may hijack the cell competition mechanism, leading to tumour initiation.

Keywords: Cell competition; supercompetition; cell fitness; homeostasis; development; cancer

Figure 1. Distinct modes of cell competition based on cell–cell contact requirement (direct or indirect) and the genotype of winner and loser cells. (a) Polarity deficient cells such as scrib mutant cells are eliminated through direct cell–cell contact. Wild‐type winner cells restrict EGFR signalling pathway in mutated cells promoting their elimination in a JNK‐dependent manner, via trans‐interaction of Sas‐PTP10D. (b) Supercompetitor Myc cells eliminate wild‐type cells trough cell intercalation. Myc‐driven cell mixing increases the surface of contact between winner and loser cells, promoting the elimination of the later through direct cell fitness comparison in a Flower (Fwe)‐dependent manner. Loser cells express the Fwe lose isoform which leads to the activation of the fitness sensor, azot, inducing hid‐dependent apoptosis. The secreted protein Sparc is expressed by these cells to provide protection to those that are only transiently unfit. (c) Reduction of survival factor/receptor levels and impairment of signalling transduction turns cells into losers. Downregulation of Dpp signalling pathway allows the transcriptional activation of brinker (brk), resulting in JNK‐dependent apoptosis. (d) The mutationally activated form of Ras oncogene (RasV12) fosters clonal expansion by compressing the neighbour wild‐type cells. These cells with less resistance to mechanical stress downregulate EGFR/ERK signalling pathway, allowing the expression of the pro‐apoptotic gene, hid. Note that in indirect cell competition (c and d) the elimination of less fit cells does not require direct contact with winners.
Figure 2. Impact of injury‐induced cell competition in adult homeostasis. (a) The injury of Drosophila adult brain induces proliferation and differentiation of quiescent adult neural progenitor cells, originating new neurons. Upon direct fitness comparison with neighbour fitter neurons, unfit neurons are eliminated by apoptosis. (b) Maintenance of epidermal stem cells (SC) with higher levels of COL17A1 (COL17A1high) via symmetric cell division (SCD) of these winner SC and asymmetric cell division (ACD) of COL17A1 low levels (COL17A1low) loser SC guarantees the homeostasis of the skin. Upon skin excision, ACD of fitter SC ensures wound healing efficiency.
Figure 3. The effect of external factors on cell competition. (a) In the intestinal and pancreatic epithelia, RasV12‐transformed cells are identified as losers by the wild‐type cells and eliminated apically. This mechanism called Epithelial Defence Against Cancer is blocked when mice are kept on high‐fat diet, potentiating the development of tumours. (b) In the hematopoietic system, differences in p53 levels trigger cell competition upon irradiation, where p53‐deficient cells outcompete wild‐type cells that acquire senescence‐like state. Homeostatic stress does not induce cell competition based on p53 levels.


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Further Reading

Baker NE (2017) Mechanisms of cell competition emerging from Drosophila studies. Current Opinion in Cell Biology 48: 40–46. DOI: 10.1016/j.ceb.2017.05.002.

Díaz‐Díaz C and Torres M (2019) Insights into the quantitative and dynamic aspects of cell competition. Current Opinion in Cell Biology 60: 68–74. DOI: 10.1016/j.ceb.2019.04.003.

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Levayer R and Moreno E (2016) How to be in a good shape? The influence of clone morphology on cell competition. Communicative and Integrative Biology 9 (1): 1–4. DOI: 10.1080/19420889.2015.1102806.

Nagata R and Igaki T (2018) Cell competition: emerging mechanisms to eliminate neighbors. Development Growth and Differentiation 60 (9): 522–530. DOI: 10.1111/dgd.12575.

Tonnessen‐Murray CA, Lozano G and Jackson JG (2017) The regulation of cellular functions by the p53 protein: cellular senescence. Cold Spring Harbor Perspectives in Medicine 7 (2): 1–14.

Vishwakarma M and Piddini E (2020) Outcompeting cancer. Nature Reviews Cancer 20: 187–198. DOI: 10.1038/s41568‐019‐0231‐8.

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Costa, Catarina Marçal, Brás‐Pereira, Catarina, and Moreno, Eduardo(Dec 2020) Cell Competition. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0028476]