Cell Competition and Its Role in the Regulation of Cell Fitness from Development to Cancer

Gregorio, Aida Di; Bowling, Sarah; Rodríguez, Tristan A.

doi:10.1016/j.devcel.2016.08.012

Cited by 157 publications

(104 citation statements)

References 98 publications

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“…Cell competition is a contact-dependent cellcell interaction mechanism that eliminates slowly dividing cells or damaged cells with tumorigenesis potential, a mechanism that can sometimes be hijacked by tumor cells to expand at the expense of wild-type (WT) neighbors (43,44) (Fig. 5A).…”

Section: Manipulation Of Neighboring Cells To Study Cell-cell Competimentioning

confidence: 99%

Development of an optimized synthetic Notch receptor as an in vivo cell–cell contact sensor

Huang

Perrimon

2017

Proc. Natl. Acad. Sci. U.S.A.

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Detection and manipulation of direct cell-cell contact in complex tissues is a fundamental and challenging problem in many biological studies. Here, we report an optimized Notch-based synthetic receptor (synNQ) useful to study direct cell-cell interactions in Drosophila. With the synNQ system, cells expressing a synthetic receptor, which contains Notch activation machinery and a downstream transcriptional activator, QF, are activated by a synthetic GFP ligand expressed by contacting neighbor cells. To avoid cis-inhibition, mutually exclusive expression of the synthetic ligand and receptor is achieved using the "flippase-out" system. Expression of the synthetic GFP ligand is controlled by the Gal4/UAS system for easy and broad applications. Using synNQ, we successfully visualized cell-cell interactions within and between most fly tissues, revealing previously undocumented cell-cell contacts. Importantly, in addition to detection of cells in contact with one another, synNQ allows for genetic manipulation in all cells in contact with a targeted cell population, which we demonstrate in the context of cell competition in developing wing disks. Altogether, the synNQ genetic system will enable a broad range of studies of cell contact in developmental biology.

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Section: Manipulation Of Neighboring Cells To Study Cell-cell Competimentioning

confidence: 99%

Development of an optimized synthetic Notch receptor as an in vivo cell–cell contact sensor

Huang

Perrimon

2017

Proc. Natl. Acad. Sci. U.S.A.

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“…This is also a key trait of cancer, where clonal growth is promoted as a response to active selection [72,73]. MYC activation is considered a hallmark of cancer initiation and maintenance [74], and the discovery of MYC function in CC has primed a series of speculations about a possible role for this phenomenon in cancer [71,75,76,77,78]. Tumours undergo continuous genetic diversification and epigenetic plasticity followed by clonal selection and expansion, revealing a genetic architecture reminiscent of Darwin’s evolutionary trees [79].…”

Section: Myc Cell Competition and Cancermentioning

confidence: 99%

MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad

Giacomo

Sollazzo

Paglia

et al. 2017

Genes

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Deregulation of MYC family proteins in cancer is associated with a global reprogramming of gene expression, ultimately promoting glycolytic pathways, cell growth, and proliferation. It is well known that MYC upregulation triggers cell-autonomous apoptosis in normal tissues, while frankly malignant cells develop resistance to apoptotic stimuli, partly resulting from MYC addiction. As well as inducing cell-autonomous apoptosis, MYC upregulation is able to trigger non cell-autonomous apoptotic death through an evolutionarily conserved mechanism known as “cell competition”. With regard to this intimate and dual relationship between MYC and cell death, recent evidence obtained in Drosophila models of cancer has revealed that, in early tumourigenesis, MYC upregulation guides the clonal expansion of mutant cells, while the surrounding tissue undergoes non-cell autonomous death. Apoptosis inhibition in this context was shown to restrain tumour growth and to restore a wild-type phenotype. This suggests that cell-autonomous and non cell-autonomous apoptosis dependent on MYC upregulation may shape tumour growth in different ways, soliciting the need to reconsider the role of cell death in cancer in the light of this new level of complexity. Here we review recent literature about MYC and cell competition obtained in Drosophila, with a particular emphasis on the relevance of cell death to cell competition and, more generally, to cancer. Possible implications of these findings for the understanding of mammalian cancers are also discussed.

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“…by generating an age-associated, neoplastic-prone tissue landscape [3]. Similarly, Henry et al have reported that aging-associated inflammation promotes selection for adaptive oncogenic events in B cell progenitors [2]; it was proposed that cell competition may in fact drive the emergence of oncogenically altered cells in a background of age-induced decline in tissue fitness, in a process that has been referred to as “adaptive oncogenesis” [4, 6]. …”

Section: Introductionmentioning

confidence: 99%

Caloric restriction delays early phases of carcinogenesis via effects on the tissue microenvironment

et al. 2017

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Caloric restriction (CR) is an effective and consistent means to delay aging and the incidence of chronic diseases related to old age, including cancer. However, the precise mechanisms responsible for the beneficial effect of CR on carcinogenic process are yet to be identified.In the present studies the hypothesis was tested that the CR might delay carcinogenesis via modulatory effects exerted on the age-associated, neoplastic-prone tissue microenvironment. Using a well characterized, orthotopic cell transplantation (Tx) system in the rat, preneoplastic hepatocytes isolated from liver nodules were injected into either old syngeneic rats fed ad libitum (AL) or animals of the same age given a CR diet (70% of AL feeding). Analysis of donor-derived cell clusters performed at 10 weeks post-Tx revealed a significant shift towards smaller class sizes in the group receiving CR diet. Clusters comprising more than 50 cells, including large hepatic nodules, were thrice more frequent in AL vs. CR animals. Incidence of spontaneous endogenous nodules was also decreased by CR. Markers of cell senescence were equally expressed in the liver of AL and CR groups. However, higher levels of SIRT1 and FOXO1 proteins were detected in CR-exposed livers, while expression of HDAC1 and C/EBPβ were decreased. These results are interpreted to indicate that CR delays the emergence of age-associated neoplastic disease through effects exerted, at least in part, on the tissue microenvironment. Nutrient-sensing pathways might mediate such modulatory effect.

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Cell Competition and Its Role in the Regulation of Cell Fitness from Development to Cancer

Cited by 157 publications

References 98 publications

Development of an optimized synthetic Notch receptor as an in vivo cell–cell contact sensor

Development of an optimized synthetic Notch receptor as an in vivo cell–cell contact sensor

MYC, Cell Competition, and Cell Death in Cancer: The Inseparable Triad

Caloric restriction delays early phases of carcinogenesis via effects on the tissue microenvironment

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