Nuclear envelope rupture drives genome instability in cancer

Lim, Sanghee; Quinton, Ryan J.; Ganem, Neil J.

doi:10.1091/mbc.e16-02-0098

Cited by 50 publications

(48 citation statements)

References 33 publications

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“…However, this explanation was not suitable for cardiac myocytes, which belong to postmitotic Cells 2020, 9, 712 9 of 14 cells. Several other observations have recently been made that disprove the assertion that invasion of mitochondria to the nucleus occurs when the nuclear membrane is disassembled during mitosis [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

“…The observations, first made already in the middle of the 20th century of mitochondria inside a nucleus, are no longer considered an artifact of electron microscopy technique [42]. On the basis of a great number of immunofluorescence assays in which brief disruption of the nuclear membrane in interphase nuclei was observed in association with various diseases and abnormal conditions [18,[22][23][24][25] as well as in healthy cells [26,43], the presence of mitochondria in the nucleoplasm is usually considered as a result of catastrophic loss of the barrier function of the nuclear membrane that might be a contributing factor of disease progression [44]. In some reports, the penetration of mitochondria into the nucleus was believed to occur due only to a mechanical process [12,44].…”

Section: Discussionmentioning

confidence: 99%

“…Using immunofluorescence techniques, it has been shown that a brief opening of the nuclear membrane can occur in the interphase nucleus. Nuclear membrane remodeling was found during viral infections [13][14][15], laminopathy [16][17][18], muscular dystrophy, cardiomyopathy, lipodystrophy [19,20], Hutchinson-Gilford progeria syndrome [21], and cancerogenesis [18,[22][23][24][25]. However, it may be premature to consider this phenomenon as specific for pathological processes only.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria in the Nuclei of Rat Myocardial Cells

Eldarov

Vangely

Vays

et al. 2020

Cells

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Electron microscopic study of cardiomyocytes taken from healthy Wistar and OXYS rats and naked mole rats (Heterocephalus glaber) revealed mitochondria in nuclei that lacked part of the nuclear envelope. The direct interaction of mitochondria with nucleoplasm is shown. The statistical analysis of the occurrence of mitochondria in cardiomyocyte nuclei showed that the percentage of nuclei with mitochondria was roughly around 1%, and did not show age and species dependency. Confocal microscopy of normal rat cardiac myocytes revealed a branched mitochondrial network in the vicinity of nuclei with an organization different than that of interfibrillar mitochondria. This mitochondrial network was energetically functional because it carried the membrane potential that responded by oscillatory mode after photodynamic challenge. We suggest that the presence of functional mitochondria in the nucleus is not only a consequence of certain pathologies but rather represents a normal biological phenomenon involved in mitochondrial/nuclear interactions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondria in the Nuclei of Rat Myocardial Cells

Eldarov

Vangely

Vays

et al. 2020

Cells

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“…The nuclear envelope (NE) is a bi-layer membrane that separates the nucleus with the chromosomes from the rest of the cellular compartments [10] and contains a large number of membrane proteins with sophisticated roles and functions [11][12][13][14]. The structure and condition of the NE is of huge importance as it has been related to viral infections [15][16][17][18][19], Muscular dystrophy [20], Cancer [21][22][23][24][25], Osteoporosis [26], Cardiovascular diseases [27][28][29], other diseases [30][31][32], and ageing [33][34][35]. Therefore, algorithms for the segmentation, visualisation and analysis of the NE could provide parameters to understand the conditions of health and disease of a cell.…”

Section: Introductionmentioning

confidence: 99%

Semantic Segmentation of HeLa Cells: An Objective Comparison between one Traditional Algorithm and Three Deep-Learning Architectures

Karabağ

Jones

Peddie

et al. 2020

Preprint

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In this work, images of a HeLa cancer cell were semantically segmented with one traditional image-processing algorithm and three deep learning architectures: VGG16, ResNet18 and Inception-ResNet-v2. Three hundred slices, each 2000 × 2000 pixels, of a HeLa Cell were acquired with Serial Block Face Scanning Electron Microscopy. The deep learning architectures were pre-trained with ImageNet and then fine-tuned with transfer learning. The image-processing algorithm followed a pipeline of several traditional steps like edge detection, dilation and morphological operators. The algorithms were compared by measuring pixel-based segmentation accuracy and Jaccard index against a labelled ground truth. The results indicated a superior performance of the traditional algorithm (Accuracy = 99%, Jaccard = 93%) over the deep learning architectures: VGG16 (93%, 90%), ResNet18 (94%, 88%), Inception-ResNet-v2 (94%, 89%).

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“…Thus while in some cell types nuclear shape and genome organization are robust to deformation, in other cell types the nucleus is highly deformable.The importance of maintaining nuclear shape for cell, tissue, and organism homeostasis is highlighted by the fact that changes in nuclear morphology and genome organization are associated with cancer 4, 26 . For example, nuclear rupture is frequently an oncogenic event 27,28 . Indeed, pathologists have used nuclear shape as a diagnostic for over a century 29 .…”

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confidence: 99%

Epithelial-Mesenchymal Plasticity is regulated by inflammatory signalling networks coupled to cell morphology

Arias-Garcia

Rickman

Sero

et al. 2019

Preprint

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The shape, size, and architecture of the nucleus determines the output of transcriptional programmes. As such, the ability of the nucleus to resist deformation and maintain its shape is essential for homeostasis. Conversely, changes in nuclear shape can alter transcription and cell state. The ability of cells to deform their nuclei is also essential for cells to invade confined spaces. But how cells set the extent of nuclear deformability in response to their environment is unclear. Here we show that the cell-cell adhesion protein JAM3 regulates nuclear shape. In epithelial cells, JAM3 is required for maintenance of nuclear shape by organizing microtubule polymers and promoting LMNA stabilization in the nuclear membrane. Depletion of JAM3 in normal epithelial cells leads to dysmorphic nuclei, which leads to differentiation into a mesenchymal-like state. Inhibiting the actions of kinesins in JAM3 depleted cells restores nuclear morphology and prevents differentiation into the mesenchymal-like state. Critically, JAM3 expression is predictive of disease progression. Thus JAM3 is a molecule which allows cells to control cell fates in response to the presence of neighbouring cells by tuning the extent of nuclear deformability. 3 IntroductionNuclear shape, size and architecture define the biophysics of key cellular processes such as transcription, replication, mRNA export, and DNA damage repair 1-4 . But nuclei are malleable viscoelastic structures 5, 6 that are frequently being stretched, strained, and compressed both by extracellular forces 7 , and the internal cytoskeleton 8-12 . Mechanisms have evolved to maintain nuclear shape and genome organization when cells are exposed to these forces 13 .Indeed, dysregulation of nuclear shape is coincident with numerous diseases including: muscular dystrophies, heart disease, and aging disorders such as progeria [14][15][16][17][18] . Thus in many cells, maintaining nuclear shape is essential for homeostasis.But while clearly maintenance of nuclear shape, size, and genome organization is essential for cellular homeostasis, transcriptional programmes that alter cell fate can be engaged by altering nuclear morphology and architecture 1,5,[19][20][21][22] . For example, nuclei undergo extensive shape changes that drive differentiation during development 23 . One means by which alteration in nuclear shape affects transcription is by affecting the nuclear translocation dynamics of transcription factors such as YAP/TAZ and NF-κB 24, 25 . Thus while in some cell types nuclear shape and genome organization are robust to deformation, in other cell types the nucleus is highly deformable.The importance of maintaining nuclear shape for cell, tissue, and organism homeostasis is highlighted by the fact that changes in nuclear morphology and genome organization are associated with cancer 4, 26 . For example, nuclear rupture is frequently an oncogenic event 27,28 . Indeed, pathologists have used nuclear shape as a diagnostic for over a century 29 . Irregular nuclear shapes and sizes are hall...

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Nuclear envelope rupture drives genome instability in cancer

Cited by 50 publications

References 33 publications

Mitochondria in the Nuclei of Rat Myocardial Cells

Mitochondria in the Nuclei of Rat Myocardial Cells

Semantic Segmentation of HeLa Cells: An Objective Comparison between one Traditional Algorithm and Three Deep-Learning Architectures

Epithelial-Mesenchymal Plasticity is regulated by inflammatory signalling networks coupled to cell morphology

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