Polyploid mitosis and depolyploidization promote chromosomal instability and tumor progression in a Notch-induced tumor model

Wang, Xianfeng; Yang, Sheng-An; Gong, Shangyu; Chang, Chien-Hung; Portilla, Juan Martin; Chatterjee, Deeptiman; Irianto, Jerome; Bao, Hongcun; Huang, Yi-Chun; Deng, Wu-Min

doi:10.1016/j.devcel.2021.05.017

Cited by 25 publications

(24 citation statements)

References 88 publications

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“…Although the causal relationship between aneuploidy and tumors is uncertain at present, studies have found that aneuploid cells with genomic instability may even exhibit the ability to proliferate indefinitely, similar to cancerous cells [70,74,75]. A recent study found that induction of Notch signaling in polyploid cells leads to malignant proliferation, loss of cell polarity, and further development into tumors with high genomic instability [76]. Interestingly, our study shows that genes associated with the Notch signaling pathway are abnormally expressed in aneuploidy Drosophila (Figures 2D and 3), suggesting a close association between aneuploidy and tumor formation.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Zhang

Huang

Zhang

et al. 2021

Genes

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Aneuploidy, which disrupts the genetic balance due to partial genome dosage changes, is usually more detrimental than euploidy variation. To investigate the modulation of gene expression in aneuploidy, we analyzed the transcriptome sequencing data of autosomal and sex chromosome trisomy in Drosophila. The results showed that most genes on the varied chromosome (cis) present dosage compensation, while the remainder of the genome (trans) produce widespread inverse dosage effects. Some altered functions and pathways were identified as the common characteristics of aneuploidy, and several possible regulatory genes were screened for an inverse dosage effect. Furthermore, we demonstrated that dosage changes of inverse regulator Inr-a/pcf11 can produce a genome-wide inverse dosage effect. All these findings suggest that the mechanism of genomic imbalance is related to the changes in the stoichiometric relationships of macromolecular complex members that affect the overall function. These studies may deepen the understanding of gene expression regulatory mechanisms.

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Section: Discussionmentioning

confidence: 99%

Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Zhang

Huang

Zhang

et al. 2021

Genes

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“…Accordingly, data obtained from synthetic autotetraploid plants (watermelon, soybean, and Arabidopsis) also indicate that polyploidy shifts the A-to-B chromatin balance toward the actively transcribed A-chromatin [ 106 , 107 ]. Moreover, recent studies provide evidence that genome duplications reorganize topologically associated domains (TAD) packaged within A- and B-chromatin compartments via the increase in intra-TAD interaction and reorganization of chromatin loops [ 106 , 108 ]. In addition, polyploidy in giant cancer cells can enlarge chromosome territories [ 109 ].…”

Section: Myc and Polyploidy Promote Chromatin Openingmentioning

confidence: 99%

Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring

Anatskaya

Vinogradov

2022

IJMS

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Polyploid cells demonstrate biological plasticity and stress adaptation in evolution; development; and pathologies, including cardiovascular diseases, neurodegeneration, and cancer. The nature of ploidy-related advantages is still not completely understood. Here, we summarize the literature on molecular mechanisms underlying ploidy-related adaptive features. Polyploidy can regulate gene expression via chromatin opening, reawakening ancient evolutionary programs of embryonality. Chromatin opening switches on genes with bivalent chromatin domains that promote adaptation via rapid induction in response to signals of stress or morphogenesis. Therefore, stress-associated polyploidy can activate Myc proto-oncogenes, which further promote chromatin opening. Moreover, Myc proto-oncogenes can trigger polyploidization de novo and accelerate genome accumulation in already polyploid cells. As a result of these cooperative effects, polyploidy can increase the ability of cells to search for adaptive states of cellular programs through gene regulatory network rewiring. This ability is manifested in epigenetic plasticity associated with traits of stemness, unicellularity, flexible energy metabolism, and a complex system of DNA damage protection, combining primitive error-prone unicellular repair pathways, advanced error-free multicellular repair pathways, and DNA damage-buffering ability. These three features can be considered important components of the increased adaptability of polyploid cells. The evidence presented here contribute to the understanding of the nature of stress resistance associated with ploidy and may be useful in the development of new methods for the prevention and treatment of cardiovascular and oncological diseases.

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“…These studies reveal a blurring of the lines between what constitutes a bona fide meiosis versus a meiosis-like process. Similar ploidy reduction processes occur in polyploid cancer cells where meiosis and recombination genes are again implicated, suggesting that related depolyploidization mechanisms occur across eukaryotes [ 2 , 3 ]. For example, a number of meiosis-specific genes (including DMC1, SPO11, and REC8) have been found to be activated during depolyploidization of polyploid tumor cells [ 36 ].…”

Section: What Drives Ploidy Changes In Pathogenic Fungi?mentioning

confidence: 99%

“…For example, increased ploidy levels frequently occur in certain organs of both animals and plants [ 1 ]. In many human tumors, especially some high-grade tumors, changes in ploidy are common and have been suggested to contribute to tumorigenesis [ 2 , 3 ]. Human fungal pathogens are a major threat to human health and cause not only superficial diseases but also life-threatening invasive or systemic infections.…”

Section: Introductionmentioning

confidence: 99%

Ploidy changes in human fungal pathogens: Going beyond sexual reproduction

Zheng

Bennett

et al. 2022

PLoS Pathog

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Polyploid mitosis and depolyploidization promote chromosomal instability and tumor progression in a Notch-induced tumor model

Cited by 25 publications

References 88 publications

Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Modulation of Global Gene Expression by Aneuploidy and CNV of Dosage Sensitive Regulatory Genes

Polyploidy and Myc Proto-Oncogenes Promote Stress Adaptation via Epigenetic Plasticity and Gene Regulatory Network Rewiring

Ploidy changes in human fungal pathogens: Going beyond sexual reproduction

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