Review
The competitive nature of cells

https://doi.org/10.1016/j.yexcr.2005.03.017Get rights and content

Abstract

The possibility that cells of multicellular organisms may compete with one another has been postulated several times. It was experimentally confirmed in Drosophila, probably for the first time, when cells with different metabolic rates were mixed: cells that would have been viable on their own disappeared due to the presence of metabolically more active cells. After almost 30 years of neglect, genetic analysis in Drosophila has started to reveal a gene network that regulates the competitive behavior of cells. If the genes regulating cellular competitiveness in Drosophila have a conserved function in mammals, the study of cell competition could have an impact in several biomedical fields, including functional degeneration, cancer, or stem cell therapies.

Section snippets

A genetic network for cell competitiveness

The possibility that cells of multicellular organisms may compete with one another has been postulated several times over the past two centuries. In 1888, Wilhelm Roux proposed the idea of a cellular struggle for survival during development [1]. Wilhelm Roux transferred Charles Darwin's theory of the struggle for existence to the fight among cells and “parts” of the organism in the process of ontogenesis. As evidence for the conflict between cell types, he referred to pathological processes in

Revealing cellular fitness

The surest foundation is quality.”

Andrew Carnegie.

To achieve epigenetic modulation, cell competition must be enabled genetically. But by what means is cell competitiveness assessed and compared from cell to cell? Some of the genes involved in this process are starting to be identified, and it appears that endocytic internalization of extracellular ligands could be one of the principles by which cell competition is implemented on a population basis [6].

While endocytosis has traditionally been

Stem cells and cell competition

Should I stay or should I go now?

If I go there will be trouble…

And if I stay it will be double!!!!

“Combat Rock”. The Clash, 1982

Adult stem cells are often found at specific locations called niches that provide the special tissue microenvironment required for the stem cell to maintain a stable undifferentiated state [33], [34], [35]. Very much like a young girl in the dilemma to leave the family house, the daughters of proliferating stem cells must face the fate decision whether to remain in the

Acknowledgments

We thank O. Fernandez-Capetillo and C. Rhiner for reading the manuscript and suggestions. Work is supported by a Caja Madrid-CNIO junior group leader grant to EM.

References (44)

  • M. Milan et al.

    Short-range cell interactions and cell survival in the Drosophila wing

    Dev. Cell.

    (2002 Jun.)
  • T. Adachi-Yamada et al.

    Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients

    Dev. Biol.

    (2002 Nov. 1)
  • E. Moreno et al.

    Evolution of TNF signaling mechanisms. JNK-dependent apoptosis triggered by Eiger, the Drosophila homolog of the TNF superfamily

    Curr. Biol.

    (2002 Jul. 23)
  • J. Secombe et al.

    Myc: a weapon of mass destruction

    Cell

    (2004 Apr. 16)
  • T.D. Donaldson et al.

    Cancer cell biology: Myc wins the competition

    Curr. Biol.

    (2004 Jun. 8)
  • G.Q. Daley

    Chronic myeloid leukemia: providing ground for cancer stem cells

    Cell

    (2004 Oct. 29)
  • E. Fuchs et al.

    Socializing with the neighbors: stem cells and their niche

    Cell

    (2004 Mar. 19)
  • E. Wieschaus et al.

    The development and function of the female germ line in Drosophila melanogaster: a cell lineage study

    Dev. Biol.

    (1979 Jan.)
  • T. Xie et al.

    Decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary

    Cell

    (1998 Jul. 24)
  • W. Roux

    Der Kampf der Theile im Organismus

    (1881)
  • D. Purves

    Neuronal competition

    Nature

    (1980 Oct. 16)
  • M.C. Raff

    Social controls on cell survival and cell death

    Nature

    (1992 Apr. 2)
  • Cited by (40)

    • Apoptotic Cell Clearance in Development

      2015, Current Topics in Developmental Biology
    • Competitive cell interactions in cancer: A cellular tug of war

      2013, Trends in Cell Biology
      Citation Excerpt :

      An important notion that has emerged from several studies is that mutations in many oncogenes or tumor-suppressor genes have the ability to alter the competitive status of cells, turning them into ‘losers’ [9,11–15] or ‘winners’ [8,10,16–21] (supercompetitors) with respect to normal cells. The correlation between cancer genes and cell competition has led to the hypothesis that competitive cell interactions may play a key role during cancer formation [7,22–26]. Indeed, several reports indicate that normal and precancerous cells can engage in hostile interactions.

    • Competitive interactions of cancer cells and normal cells via secretory microRNAs

      2012, Journal of Biological Chemistry
      Citation Excerpt :

      Competitive interactions among cells are the basis of many homeostatic processes in biology. In Drosophila, normal epithelial cells compete with transformed ones for individual survival, which is a process called cell competition (1, 2). If a given group of cells was exposed to some stress, it would be separated into subpopulations of cells with different levels of damage.

    • Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila

      2010, Developmental Cell
      Citation Excerpt :

      We do not yet know how the alternative splicing is regulated. The simplest possibility is that when cells competing unsuccessfully for extracellular resources are deprived of survival factors (Diaz and Moreno, 2005), they are also depleted from some crucial splicing factors and default splicing will result in the formation of the normally repressed Lose forms. The observation that fweLose upregulation was usually detected throughout the entire loser clone and not just at clone borders could be the consequence of a mechanism that propagates the “loser” state in outcompeted clones.

    View all citing articles on Scopus
    View full text