Movatterモバイル変換

[0]ホーム
URL:

Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
Thehttps:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

NIH NLM Logo
Log inShow account info
Access keysNCBI HomepageMyNCBI HomepageMain ContentMain Navigation
pubmed logo
Advanced Clipboard
User Guide

Full text links

Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Full text links

Actions

Share

Review
.2013 Mar 18;200(6):689-98.
doi: 10.1083/jcb.201301051.

Mechanisms of cell competition: themes and variations

Affiliations
Review

Mechanisms of cell competition: themes and variations

Romain Levayer et al. J Cell Biol..

Abstract

Cell competition is the short-range elimination of slow-dividing cells through apoptosis when confronted with a faster growing population. It is based on the comparison of relative cell fitness between neighboring cells and is a striking example of tissue adaptability that could play a central role in developmental error correction and cancer progression in both Drosophila melanogaster and mammals. Cell competition has led to the discovery of multiple pathways that affect cell fitness and drive cell elimination. The diversity of these pathways could reflect unrelated phenomena, yet recent evidence suggests some common wiring and the existence of a bona fide fitness comparison pathway.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Mutations and pathways involved in cell competition and intrinsic tumor suppression have a context-dependent phenotype. (A) In “classical” cell competition, mutant cells (light green) surrounded by cells with the same genotype survive (top), whereas they are eliminated when surrounded by wt cells (white cells, bottom). Subsequently, wt cells replenish the tissue by compensatory proliferation. Green cells are the mutant cells, purple cells are the winners. (B) Mutation/pathways that induce a reduction of fitness leading to cell competition and intrinsic tumor suppression. (C) Supercompetitor cells (light purple) do not induce apoptosis when surrounded by cells with the same genotype (top), whereas they can grow at the expense of the surrounding wt cells (white) by inducing their death (bottom). Winner cell growth is up-regulated by compensatory proliferation, through the secretion of Dpp, Wg, Hh, and Unpaired from dying cells (dark gray arrow), or the non–cell autonomous down-regulation of Hippo pathway induced by dying cells (not depicted). Purple cells are the winner cells, green cells are the loser cells. (D) Mutation/pathways that induce an increase of fitness, thereby generating supercompetitors.
Figure 2.
Figure 2.
Cell competition and cell selection are multistep processes. Schematic of the multiple layers of regulation involved in loser cell elimination. Colored rectangles separate each hypothetical layer of control. Cell selection is initiated by mutations/pathways leading to a gain or a loss of fitness (light purple). The modulation of fitness leads to the deficit/gain of some limiting factors for which cells are competing (bottleneck, dark green). This then activates cell fitness markers (Flower, Sparc; yellow). Eventually, loser cell elimination is induced by different cell autonomous signal (JNK, Hid; light green), and by signals emitted by winner cells (dark purple). Hypothetical epistatic relationships are marked by broken lines.
Figure 3.
Figure 3.
Different scenarios regarding the requirement of loser cell engulfment. (A) Engulfment of loser cells (green) by winner cells (purple) is required for their elimination. Engulfment is induced by JNK activation in winner cells, which in turn activates the engulfment-specific gene PVR. Engulfment also requires the presence of WASP, Draper, PSR, ELMO, and Mbc. Winner cell lysosomes contain fragments of loser cells (green particles). (B) Alternatively, engulfment is not required for loser cell elimination, but only for the clearance of already delaminated apoptotic corpses. This is achieved by macrophages (blue) through Draper activation and, potentially, WASP.
Figure 4.
Figure 4.
The diffusible killing signal and the transmembrane receptor–dependent hypothesis. (A) Loser cell death is induced by an unknown short-range diffusing signal produced by winner cells. The killing signal (orange dots) diffuses on short range and activates apoptosis two to three cell diameters away from winner cells, whereas cells located farther survive (“survival”). Only cells with a fitness deficit respond to the signal (here, depicted by the presence of a green receptor on loser cells). The winners are in purple and the losers in green. (B) Loser cell elimination is induced by a direct contact with winner cells. An uncharacterized receptor in the winner cells (purple transmembrane protein) recognizes Flowerlose (Fwelose, green transmembrane protein) or the absence of Flowerubi and activates a contact-dependent killing signal (interaction between brown ligand and dark green receptor). The winners are in purple and the losers in green. (C) Combined model where winner/loser contact is required for fitness comparison (through Flower code), which then induces the production of a diffusible killing signal in the contacting winners. Only cells with a fitness deficit (green receptor) are sensitive to the killing signal. The winners are in purple and the losers in green.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abrams J.M. 2002. Competition and compensation: coupled to death in development and cancer. Cell. 110:403–406 10.1016/S0092-8674(02)00904-2 - DOI - PubMed
    1. Adachi-Yamada T., O’Connor M.B. 2002. Morphogenetic apoptosis: a mechanism for correcting discontinuities in morphogen gradients. Dev. Biol. 251:74–90 10.1006/dbio.2002.0821 - DOI - PubMed
    1. Adachi-Yamada T., Fujimura-Kamada K., Nishida Y., Matsumoto K. 1999. Distortion of proximodistal information causes JNK-dependent apoptosis in Drosophila wing. Nature. 400:166–169 10.1038/22112 - DOI - PubMed
    1. Arbouzova N.I., Zeidler M.P. 2006. JAK/STAT signalling in Drosophila: insights into conserved regulatory and cellular functions. Development. 133:2605–2616 10.1242/dev.02411 - DOI - PubMed
    1. Baena-Lopez L.A., Nojima H., Vincent J.P. 2012. Integration of morphogen signalling within the growth regulatory network. Curr. Opin. Cell Biol. 24:166–172 10.1016/j.ceb.2011.12.010 - DOI - PubMed

Publication types

MeSH terms

Related information

LinkOut - more resources

Full text links
Silverchair Information Systems full text link Silverchair Information Systems Free PMC article
Cite
Send To

NCBI Literature Resources

MeSHPMCBookshelfDisclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

[8]ページ先頭
©2009-2025 Movatter.jp