Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis

Clemente‐Ruiz, Marta; Murillo‐Maldonado, Juan Manuel; Benhra, Najate; Barrio, Lara; Pérez, Lídia; Quiroga, Gonzalo; Nebreda, Ángel R.; Milán, Marco

doi:10.1016/j.devcel.2016.01.008

Cited by 54 publications

(80 citation statements)

References 30 publications

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“…ROS can also lead to proteomic damage and thus potentially contributes to the proteotoxic stress discussed earlier. Interestingly, in a Drosophila model of aneuploidy, ROS play a role in activating a JNK-dependent apoptotic clearance response (Clemente-Ruiz et al, 2016). These observations point to potential interplay between different types of stress experienced by aneuploid cells and suggest that molecular signals generated by these stress states may help tissues eliminate aneuploid cells.…”

Section: Aneuploidy-associated Stressmentioning

confidence: 99%

Cellular Stress Associated with Aneuploidy

et al. 2018

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Aneuploidy, chromosome stoichiometry that deviates from exact multiples of the haploid compliment of an organism, exists in eukaryotic microbes, several normal human tissues, and the majority of solid tumors. Here, we review the current understanding about the cellular stress states that may result from aneuploidy. The topics of aneuploidy-induced proteotoxic, metabolic, replication, and mitotic stress are assessed in the context of the gene dosage imbalance observed in aneuploid cells. We also highlight emerging findings related to the downstream effects of aneuploidy-induced cellular stress on the immune surveillance against aneuploid cells.

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Section: Aneuploidy-associated Stressmentioning

confidence: 99%

Cellular Stress Associated with Aneuploidy

et al. 2018

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“…Tissue stem cells are responsible for the constant self-renewal of our tissues, and their behavior must be tightly regulated to prevent diseases. Contrasting with other proliferative non-stem cells [4][5][6], adult stem cells have been proposed to tolerate aneuploidy and not activate apoptosis in response to genomic instability [7][8][9][10]. This resistance to aneuploidy underscores a need to understand how tolerated aneuploidy impacts adult stem cell behavior and tissue homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Aneuploidy promotes intestinal dysplasia in Drosophila

Resende

Monteiro

Brás

et al. 2018

Preprint

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Aneuploidy is associated with different human diseases, particularly cancer, but how different cell types within tissues respond to aneuploidy is not fully understood. In some studies, aneuploidy has been shown to have a deleterious effect and lead to cell death, however it has also been shown to be a causal event of tumorigenesis in other contexts.Here, we show that Drosophila intestinal stem cells have a particular tolerance to aneuploidy and do not activate apoptosis in response to chromosome misegregation like other non-stem cells. Instead, we observe the development of tissue dysplasia characterized by an accumulation of progenitor cells, increased stem cell proliferation rate, and an excess of cells of the enteroendocrine lineage. Our findings highlight the importance of mechanisms acting to prevent aneuploidy within tissue stem cells and provide an in vivo model of how these cells can act as reservoirs for genomic alterations that can lead to dysplasia.

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“…Transcription profiles were performed at the Functional Genomics Core of IRB as previously described [71].…”

Section: Microarraymentioning

confidence: 99%

Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth inDrosophila

Sánchez

Mesquita

Ingaramo

et al. 2019

Preprint

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HIGHLIGHTS ✓ Dmp53-dependent Eiger expression is required to coordinate intra-organ growth ✓ Eiger acts through its receptor Grindelwald and JNK signaling to reduce growth and proliferation rates in a non-cell-autonomous manner ✓ Eiger/JNK-dependent Dilp8 expression coordinates intra-organ growth but not proliferation ✓ Eiger/JNK activation triggers ROS production ✓ ROS act non-cell-autonomously to regulate proliferation of adjacent epithelial cells. ABSTRACTCoordinated intra-and inter-organ growth is essential during animal development to generate individuals of proper size and shape. The Drosophila wing has been a valuable model system to reveal the existence of a stress response mechanism mediated by Drosophila p53 (Dmp53) and involved in the coordination of tissue growth between adjacent cell populations upon targeted reduction of growth rates. Here we present evidence that a two-step molecular mechanism is being used by Dmp53 to reduce in a non-autonomous manner growth and proliferation in adjacent cell populations. First, Dmp53-mediated transcriptional induction of Drosophila TNFα ligand Eiger leads to cell autonomous activation of JNK. Second, two different signaling events downstream of the Eiger/JNK axis are induced in the growth depleted territory in order to independently regulate tissue size and cell number in adjacent cell populations. Whereas expression of the systemic hormone dILP8 coordinates intra-organ growth and final tissue size, induction of Reactive Oxygen Species downstream of Eiger/JNK and, as a consequence of apoptosis induction, acts non-cellautonomously to regulate proliferation rates of adjacent epithelial cells. Our results unravel how local and systemic signals can act concertedly to coordinate growth and proliferation within an organ in order to generate well-proportioned organs and functionally integrated adults.

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Gene Dosage Imbalance Contributes to Chromosomal Instability-Induced Tumorigenesis

Cited by 54 publications

References 30 publications

Cellular Stress Associated with Aneuploidy

Cellular Stress Associated with Aneuploidy

Aneuploidy promotes intestinal dysplasia in Drosophila

Eiger/TNFα-mediated Dilp8 and ROS production coordinate intra-organ growth inDrosophila

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