Cell Competition Time Line: Winners Kill Losers, which Are Extruded and Engulfed by Hemocytes

Lolo, Fidel-Nicolás; Casas‐Tintó, Sergio; Moreno, Eduardo

doi:10.1016/j.celrep.2012.08.012

Cited by 82 publications

(83 citation statements)

References 49 publications

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“…Second, we observe that neighboring cell engulfment mediates competition between human cells. This observation is in contrast to a recent report which suggests that in Drosophila tissues, the post-apoptotic engulfment of loser cells may be mediated by hemocytes, which phagocytize cell corpses, rather than by the neighboring cells [35]. While the identity of the engulfing cells and whether engulfment itself mediates competition in Drosophila are controversial, we clearly show that neighboring cell-mediated engulfment and killing occur in mixed populations of human cells.…”

Section: Discussioncontrasting

confidence: 55%

Competition between human cells by entosis

et al. 2014

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Human carcinomas are comprised of complex mixtures of tumor cells that are known to compete indirectly for nutrients and growth factors. Whether tumor cells could also compete directly, for example by elimination of rivals, is not known. Here we show that human cells can directly compete by a mechanism of engulfment called entosis. By entosis, cells are engulfed, or cannibalized while alive, and subsequently undergo cell death. We find that the identity of engulfing ("winner") and engulfed ("loser") cells is dictated by mechanical deformability controlled by RhoA and actomyosin, where tumor cells with high deformability preferentially engulf and outcompete neighboring cells with low deformability in heterogeneous populations. We further find that activated Kras and Rac signaling impart winner status to cells by downregulating contractile myosin, allowing for the internalization of neighboring cells that eventually undergo cell death. Finally, we compute the energy landscape of cell-in-cell formation, demonstrating that a mechanical differential between winner and loser cells is required for entosis to proceed. These data define a mechanism of competition in mammalian cells that occurs in human tumors.

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Section: Discussioncontrasting

confidence: 55%

Competition between human cells by entosis

et al. 2014

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“…Nevertheless, in Minute mosaics, the small number of caspase-positive cells that are still within the epithelium at any one time are predominantly located within one or two cell diameters of the clone edge 14,20,21,71 . This suggests that the pro-apoptotic signal acts at short range (although a longer range has been suggested for myc mosaics).…”

Section: Seeking Mediators Of Cell Competitionmentioning

confidence: 99%

“…Apoptotic cells are rapidly excluded from epithelia to prevent disruption of epithelial integrity 72 . In D. melanogaster imaginal discs, dying cells accumulate at the disc basal surface 14,20,21 and are subsequently scavenged by macrophages 21 (FIG. 3b).…”

Section: Seeking Mediators Of Cell Competitionmentioning

confidence: 99%

“…However, as many of these genes encode cytoskeletal regulators, their specificity to cell competition is debatable. Moreover, the primary observation that these genes are required in winner cells for competition to occur has been challenged 21 . Even though the role of engulfment remains controversial, these studies have raised the possibility that apoptosis at mosaic boundaries may not involve a classic ligand-receptor signalling pathway.…”

Section: Engulfment Of Live Loser Cellsmentioning

confidence: 99%

“…Another, non-mutually exclusive possibility is that cell competition may be more readily detected in epithelia because of their planar organization. The discovery of cell competition and most of the sub sequent mechanistic insight came from studies of D. melano gaster appendages 13,14,[16][17][18][19][20][21][22][23] in which it is relatively easy to generate genetic mosaics 24 that confront cells with different features, including growth rates. This can be achieved, for example, by genetically reducing or boosting translational activity in a clone of cells within the tissue 13,14,25,26 .…”

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Mechanisms and mechanics of cell competition in epithelia

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Modelling Cancer in Drosophila : The Next Generation

Cheng

Parsons

Richardson

2013

Encyclopedia of Life Sciences

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Drosophila melanogaster , the vinegar fly, has been utilised as a genetic amenable model organism for more than 100 years. In recent years, its use in modelling human cancer has been greatly expanding. In this article, an update of the recent advances in Drosophila research towards understanding cancer development is provided. Genetic analysis in Drosophila has provided considerable insight into the mechanisms controlling tissue growth and cell invasion/metastasis during tumourigenesis, as well as the importance of stem cells in tissue regeneration and cancer, and how genes cooperate in tumourigenesis. Several evolutionarily conserved signalling pathways are emerging as playing key roles in many of these processes, including the Jun kinase, Notch, Wnt, Jak/Stat and the Hippo tissue growth control pathway. Drosophila has also been specifically utilised to model certain human cancers, by expression of the human versions of cancer‐causing genes, including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia. Finally, the use of Drosophila as a vehicle for anticancer drug discovery is beginning to make an important impact in combating human cancer. Key Concepts: Drosophila is a useful system for modelling human cancer due to the high conservation of critical cancer‐causing genes between humans and flies. Many signalling pathways contribute to tissue growth; however, the Hippo growth control pathway is emerging as playing a major role. The Jun kinase signalling pathway plays a context‐dependent role in invasion/metastasis. Cell polarity and differentiation factors play important roles in controlling the behaviour of stem cells, which can be usurped in cancer. Cell competition mechanisms are important in removing damaged cells, and the perturbation of this control contributes to tumourigenesis. Cancer is a cooperative process and Drosophila research has revealed many cooperating oncogenes and tumour suppressors. Drosophila provides a useful model system to investigate specific human cancers including multiple endocrine neoplasia type 2, glioblastoma and acute myeloid leukaemia. Drosophila can be utilised to screen for anticancer drugs.

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Cell Competition Time Line: Winners Kill Losers, which Are Extruded and Engulfed by Hemocytes

Cited by 82 publications

References 49 publications

Competition between human cells by entosis

Competition between human cells by entosis

Mechanisms and mechanics of cell competition in epithelia

Modelling Cancer in Drosophila : The Next Generation

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