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Nuclear Mechanics in Cancer

  • Celine Denais
  • Jan LammerdingEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 773)

Abstract

Despite decades of research, cancer metastasis remains an incompletely understood process that is as complex as it is devastating. In recent years, there has been an increasing push to investigate the biomechanical aspects of tumorigenesis, complementing the research on genetic and biochemical changes. In contrast to the high genetic variability encountered in cancer cells, almost all metastatic cells are subject to the same physical constraints as they leave the primary tumor, invade surrounding tissues, transit through the circulatory system, and finally infiltrate new tissues. Advances in live cell imaging and other biophysical techniques, including measurements of subcellular mechanics, have yielded stunning new insights into the physics of cancer cells. While much of this research has been focused on the mechanics of the cytoskeleton and the cellular microenvironment, it is now emerging that the mechanical properties of the cell nucleus and its connection to the cytoskeleton may play a major role in cancer metastasis, as deformation of the large and stiff nucleus presents a substantial obstacle during the passage through the dense interstitial space and narrow capillaries. Here, we present an overview of the molecular components that govern the mechanical properties of the nucleus, and we discuss how changes in nuclear structure and composition observed in many cancers can modulate nuclear mechanics and promote metastatic processes. Improved insights into this interplay between nuclear mechanics and metastatic progression may have powerful implications in cancer diagnostics and therapy and may reveal novel therapeutic targets for pharmacological inhibition of cancer cell invasion.

Keywords

Cytoskeleton LINC complex Mechanotransduction Mechanical stability Nuclear lamina 

Abbreviations

ER

Endoplasmic reticulum

KASH

Klarsicht, ANC-1, Syne Homology

LAPs

Lamina-associated polypeptides

LBR

Lamin B receptor

LINC

Linker of Nucleoskeleton and Cytoskeleton

NPC

Nuclear pore complex

Notes

Acknowledgements

We apologize to all authors whose work could not be cited due to space constraints. This work was supported by National Institutes of Health awards [R01 NS059348 and R01 HL082792], a National Science Foundation CAREER award to J. L. [CBET-1254846], the Department of Defense Breast Cancer Idea Award [BC102152], and an award from the Progeria Research Foundation [PRF2011-0035].

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Biomedical EngineeringWeill Institute for Cell and Molecular Biology, Cornell UniversityIthacaUSA
  2. 2.Department of Biomedical EngineeringWeill Institute for Cell and Molecular Biology, Cornell UniversityIthacaUSA

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