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Nuclear structure in cancer cells

Key Points

  • The architecture of cell nuclei is often altered in cancer cells. Specific tumour types are associated with characteristic alterations, and these provide an important diagnostic feature.

  • The nuclear matrix participates in the spatial organization of the genome and other nuclear components. The protein composition of the nuclear matrix is altered in tumour cells and these changes might be useful tumour markers.

  • Characteristic changes of nuclear shape and of chromatin texture can be induced in normal cells in vitro by oncogene activation. In vitro models will help to unravel the mechanisms by which oncogenes induce these tumour-specific nuclear changes and how these changes affect gene regulation.

  • Chromosome territories and gene loci display characteristic spatial arrangements in cell nuclei, and these have an important role in the generation of diagnostically significant translocations associated with human malignancies.

  • Structural alterations in tumour cells also include changes in nucleoli and the appearance of the perinucleolar compartment. These might be useful diagnostic markers in combination with automated imaging and image analysis.

  • The promyelocytic leukaemia (PML) protein, an essential component of PML bodies, is mislocalized in leukaemic cells of patients with acute promyelocytic leukaemia, leading to the disruption of PML bodies. Treatment with anticancer drugs leads to the reassembly of PML bodies and a reversion of the malignant phenotype.

  • High-throughput nuclear-structure-based assays to screen drugs for their ability to revert malignancy-associated nuclear changes might identify new therapeutics.

Abstract

Nuclear architecture — the spatial arrangement of chromosomes and other nuclear components — provides a framework for organizing and regulating the diverse functional processes within the nucleus. There are characteristic differences in the nuclear architectures of cancer cells, compared with normal cells, and some anticancer treatments restore normal nuclear structure and function. Advances in understanding nuclear structure have revealed insights into the process of malignant transformation and provide a basis for the development of new diagnostic tools and therapeutics.

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Figure 1: Nuclear structure in normal and cancer cells.
Figure 2: The ultrastructure of the nuclear matrix.
Figure 3: Nuclear alterations in lung cancer cells.
Figure 4: Nuclear genome organization.
Figure 5: Chromatin changes in senescent cells.
Figure 6: PML bodies.

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Acknowledgements

We are grateful to S. Huang (Northwestern University Medical School, Illinois, USA), H. de Thé (Hopital St. Louis, Paris, France), and G. S. Stein (University of Massachusetts Medical School, USA) for their help and for valuable comments on the manuscript. We thank J. Koch for support in preparing the figures. D. Z. acknowledges the VolkswagenStiftung and J. N. acknowledges the American Cancer Society and National Cancer Institute for support.

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Correspondence to Daniele Zink.

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DATABASES

Cancer.gov

acute promyelocytic leukaemia

bladder cancer

breast cancer

cervical cancer

large-cell lung cancer

prostate cancer

thyroid cancer

Entrez Gene

B23

barrier to autointegration factor 1

BCL2

emerin

hnRNP

HRAS

lamin A/C

lamin B

lamina associated polypeptide-2β

NUMA

p114

PML

RET

SATB1

FURTHER INFORMATION

Nulear Protein Database

Structure and function of the cell nucleus

Glossary

FLUORESCENCE IN SITU HYBRIDIZATION

(FISH). A procedure for detecting specific DNA or RNA sequences in fixed cells, tissues or on mitotic chromosomes. One or more fluorescently labelled DNA probes are hybridized to their DNA or RNA targets and detected by fluorescence microscopy. In one application of FISH, chromosomal translocations can be directly visualized with probes hybridized to DNA sequences at or adjacent to potential chromosomal breakpoints.

METAPHASE SPREAD

A preparation of mitotic chromosomes useful for karyotyping. The chromosomes from single cells remain together, but ideally with enough separation for each to be identified by procedures that differentially stain specific chromosome bands, or by fluorescence in situ hybridization.

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Zink, D., Fischer, A. & Nickerson, J. Nuclear structure in cancer cells. Nat Rev Cancer 4, 677–687 (2004). https://doi.org/10.1038/nrc1430

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