Mechanisms of Nuclear Size Regulation in Model Systems and Cancer

Jevtić, Predrag; Levy, Daniel L.

doi:10.1007/978-1-4899-8032-8_25

Cited by 76 publications

(110 citation statements)

References 200 publications

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“…Morphological changes in the nucleus are hallmarks of cancer cells, 6,7 and the LINC complex and nuclear lamina act to maintain nuclear structure. 36 Therefore, we focused on the shapes of the nuclei of cells with decreased levels of LINC components.…”

Section: Depletion Of Sun1 Affects Nucleolar Morphologymentioning

confidence: 99%

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Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli

Matsumoto

Sakamoto

Matsumori

et al. 2016

Nucleus

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A supervised machine learning algorithm, which is qualified for image classification and analyzing similarities, is based on multiple discriminative morphological features that are automatically assembled during the learning processes. The algorithm is suitable for population-based analysis of images of biological materials that are generally complex and heterogeneous. Here we used the algorithm wndchrm to quantify the effects on nucleolar morphology of the loss of the components of nuclear envelope in a human mammary epithelial cell line. The linker of nucleoskeleton and cytoskeleton (LINC) complex, an assembly of nuclear envelope proteins comprising mainly members of the SUN and nesprin families, connects the nuclear lamina and cytoskeletal filaments. The components of the LINC complex are markedly deficient in breast cancer tissues. We found that a reduction in the levels of SUN1, SUN2, and lamin A/C led to significant changes in morphologies that were computationally classified using wndchrm with approximately 100% accuracy. In particular, depletion of SUN1 caused nucleolar hypertrophy and reduced rRNA synthesis. Further, wndchrm revealed a consistent negative correlation between SUN1 expression and the size of nucleoli in human breast cancer tissues. Our unbiased morphological quantitation strategies using wndchrm revealed an unexpected link between the components of the LINC complex and the morphologies of nucleoli that serves as an indicator of the malignant phenotype of breast cancer cells.

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Section: Depletion Of Sun1 Affects Nucleolar Morphologymentioning

confidence: 99%

“…In particular, an enlarged nucleus, abnormal nuclear shape, anisokaryosis, increased chromatin staining, and altered nucleolar size are often observed in cancer cells. 6,7 These phenotypes are used for histological and cytological diagnosis. Further, the diagnostic and prognostic pathology of the NE in human cancers was described.…”

Section: Introductionmentioning

confidence: 99%

Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli

Matsumoto

Sakamoto

Matsumori

et al. 2016

Nucleus

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show abstract

“…61,100,170 Chromosomal gains and losses, amplification or deletion of smaller genomic fragments, and changes in higher-order chromatin structure are all associated with cancer. 171,172 Cancer-associated changes in nuclear morphology may disrupt normal chromatin positioning, gene expression, and DNA damage pathways, potentially contributing to disease progression.…”

Section: Nuclear Morphology and Diseasementioning

confidence: 99%

“…These findings are potentially relevant to cancer where deviations from normal N/C volume ratios are frequently observed. 100 Another factor that contributes to proper MBT timing in the Xenopus embryo is the ratio of DNA to cytoplasm. 121,122 By varying the DNA content or cytoplasmic volume of early X. laevis embryos, it was shown that increasing the ratio of DNA to cytoplasm resulted in an earlier MBT.…”

Section: Nuclear Size In Embryonic Developmentmentioning

confidence: 99%

“…71 Downregulation of Rtn4 Interacting Protein 1 (Rtn4IP1) has been observed in thyroid cancers, 98,99 potentially decreasing the efficiency with which Rtn4 shapes tubulated ER and leading to an increase in nuclear size. 100 As another example, Rtn1 is upregulated in malignant pancreatic carcinoma, diffusely infiltrating gliomas, and neuroendocrine tumors, 98,[101][102][103] again possibly influencing ER and nuclear morphology in these cancers.…”

Section: 76mentioning

confidence: 99%

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Recent advances in understanding nuclear size and shape

Mukherjee

Chen

Levy

2016

Nucleus

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Size and shape are important aspects of nuclear structure. While normal cells maintain nuclear size within a defined range, altered nuclear size and shape are associated with a variety of diseases. It is unknown if altered nuclear morphology contributes to pathology, and answering this question requires a better understanding of the mechanisms that control nuclear size and shape. In this review, we discuss recent advances in our understanding of the mechanisms that regulate nuclear morphology, focusing on nucleocytoplasmic transport, nuclear lamins, the endoplasmic reticulum, the cell cycle, and potential links between nuclear size and size regulation of other organelles. We then discuss the functional significance of nuclear morphology in the context of early embryonic development. Looking toward the future, we review new experimental approaches that promise to provide new insights into mechanisms of nuclear size control, in particular microfluidic-based technologies, and discuss how altered nuclear morphology might impact chromatin organization and physiology of diseased cells.

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Reprogramming nucleolar size by genetic perturbation of the extranuclear Rab GTPases Ypt6 and Ypt32

Chatterjee,

Ganguly,

Bhattacharyya

2023

FEBS Letters

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Reprogramming organelle size has been proposed as a potential therapeutic approach. However, there have been few reports of nucleolar size reprogramming. We addressed this question in Saccharomyces cerevisiae by studying mutants having opposite effects on the nucleolar size. Mutations in genes involved in nuclear functions (KAR3, CIN8, and PRP45) led to enlarged nuclei/nucleoli, whereas mutations in secretory pathway family genes, namely the Rab‐GTPases YPT6 and YPT32, reduced nucleolar size. When combined with mutations leading to enlarged nuclei/nucleoli, the YPT6 or YPT32 mutants can effectively reprogram the nuclear/nucleolar size almost back to normal. Our results further indicate that null mutation of YPT6 causes secretory stress that indirectly influences nuclear localization of Maf1, the negative regulator of RNA Polymerase III, which might reduce the nucleolar size by inhibiting nucleolar transcript enrichment.

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Mechanisms of Nuclear Size Regulation in Model Systems and Cancer

Cited by 76 publications

References 200 publications

Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli

Loss of the integral nuclear envelope protein SUN1 induces alteration of nucleoli

Recent advances in understanding nuclear size and shape

Reprogramming nucleolar size by genetic perturbation of the extranuclear Rab GTPases Ypt6 and Ypt32

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