Transcriptional versus metabolic control of cell fitness during cell competition

Lawlor, Katerina; Pérez-Montero, Salvador; Lima, Ana; Rodríguez, Tristan A.

doi:10.1016/j.semcancer.2019.05.010

Cited by 18 publications

(15 citation statements)

References 87 publications

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“…Thus, if synthetic devices perturb the genetic fitness landscape of the cell-perhaps through direct or indirect regulation of fitness genes-they may drive the selection of a subset of cells. By impacting cell fitness, synthetic devices can also change a cell's proliferation rate and metabolic profile (Lawlor et al, 2020), thus driving changes to cell state. In turn, the synthetic devices can then drive the clonal dynamics of the multicellular population and lead to unanticipated consequences.…”

Section: Cell Fate Programing and The Dynamic Cell Statementioning

confidence: 99%

Context-aware synthetic biology by controller design: Engineering the mammalian cell

2021

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Section: Cell Fate Programing and The Dynamic Cell Statementioning

confidence: 99%

Context-aware synthetic biology by controller design: Engineering the mammalian cell

2021

View full text Add to dashboard Cite

“…In Drosophila, cells heterozygous for mutations in Rp genes are selectively eliminated from mosaic imaginal discs, where they are replaced by neighboring wild type cells (Morata & Ripoll, 1975a;Simpson, 1979). This phenomenon, named 'cell competition', represents a process whereby cells that present differences from their neighbors can be eliminated from growing tissues, thought to enable the removal of cells that might be deleterious to the tissue (Morata & Ripoll, 1975a;Lawlor, Perez-Montero, Lima, & Rodriguez, 2019;Baker, 2020;Vishwakarma & Piddini, 2020;Marques-Reis & Moreno, 2021;Morata, 2021). Because Rp gene dose is likely to be affected whenever one or more chromosomes or substantial chromosome regions are monosomic, cell competition could help eliminate aneuploid cells on the basis of altered Rp gene dose (McNamee & Brodsky, 2009).…”

Section: Introductionmentioning

confidence: 99%

The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function

Kiparaki

Khan

Folgado-Marco

et al. 2022

eLife

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Ribosomal Protein (Rp) gene haploinsufficiency affects translation rate, can lead to protein aggregation, and causes cell elimination by competition with wild type cells in mosaic tissues. We find that the modest changes in ribosomal subunit levels observed were insufficient for these effects, which all depended on the AT-hook, bZip domain protein Xrp1. Xrp1 reduced global translation through PERK-dependent phosphorylation of eIF2α. eIF2α phosphorylation was itself sufficient to enable cell competition of otherwise wild type cells, but through Xrp1 expression, not as the downstream effector of Xrp1. Unexpectedly, many other defects reducing ribosome biogenesis or function (depletion of TAF1B, eIF2, eIF4G, eIF6, eEF2, eEF1α1, or eIF5A), also increased eIF2α phosphorylation and enabled cell competition. This was also through the Xrp1 expression that was induced in these depletions. In the absence of Xrp1, translation differences between cells were not themselves sufficient to trigger cell competition. Xrp1 is shown here to be a sequence-specific transcription factor that regulates transposable elements as well as single-copy genes. Thus, Xrp1 is the master regulator that triggers multiple consequences of ribosomal stresses, and is the key instigator of cell competition.

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“…Cells displaying low TEAD activity are eliminated through cell competition, thereby introducing a stringent quality control mechanism over survival of pluripotent stem cells [20] . Besides TEAD, additional transcription factors that have been repeatedly implicated in cell competition include MYC, p53, NF-κB, and STAT; however, their mechanistic role in the process is yet to be elucidated, if any [21] . On the other hand, the cell metabolic efficiency is likely to represent a basic parameter for the regulation of cell competition, as suggested by the Minute mutant phenotype referred to above.…”

Section: The Need To Assess Fitness: Quality-control Mechanismsmentioning

confidence: 99%

Cell competition, cooperation, and cancer

2021

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Complex multicellular organisms require quantitative and qualitative assessments on each of their constitutive cell types to ensure coordinated and cooperative behavior towards overall functional proficiency. Cell competition represents one of the operating arms of such quality control mechanisms and relies on fitness comparison among individual cells. However, what is exactly included in the fitness equation for each cell type is still uncertain. Evidence will be discussed to suggest that the ability of the cell to integrate and collaborate within the organismal community represents an integral part of the best fitness phenotype. Thus, under normal conditions, cell competition will select against the emergence of altered cells with disruptive behavior towards tissue integrity and/or tissue pattern formation. On the other hand, the winner phenotype prevailing as a result of cell competition does not entail, by itself, any degree of growth autonomy. While cell competition per se should not be considered as a biological driving force towards the emergence of the neoplastic phenotype, it is possible that the molecular machinery involved in the winner/loser interaction could be hijacked by evolving cancer cell populations.

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Transcriptional versus metabolic control of cell fitness during cell competition

Cited by 18 publications

References 87 publications

Context-aware synthetic biology by controller design: Engineering the mammalian cell

Context-aware synthetic biology by controller design: Engineering the mammalian cell

The transcription factor Xrp1 orchestrates both reduced translation and cell competition upon defective ribosome assembly or function

Cell competition, cooperation, and cancer

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