Advertisement

Mechanics of the Cell Nucleus

  • Dong-Hwee Kim
  • Jungwon Hah
  • Denis Wirtz
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1092)

Abstract

Nucleus is a specialized organelle that serves as a control tower of all the cell behavior. While traditional biochemical features of nuclear signaling have been unveiled, many of the physical aspects of nuclear system are still under question. Innovative biophysical studies have recently identified mechano-regulation pathways that turn out to be critical in cell migration, particularly in cancer invasion and metastasis. Moreover, to take a deeper look onto the oncologic relevance of the nucleus, there has been a shift in cell systems. That is, our understanding of nucleus does not stand alone but it is understood by the relationship between cell and its microenvironment in the in vivo-relevant 3D space.

Keywords

Nuclear mechanics Mechanotransduction Nuclear lamina Nuclear envelope Nucleoskeleton 

Notes

Acknowledgments

Authors are indebted to many colleagues and students for their input and perspectives of nuclear mechanics. Special thanks to Dr. Denis Wirtz at the Johns Hopkins University, who provided overall guidance of this chapter. We appreciated Geonhui Lee, Seong-Beom Han, Jung-Won Park, and Jeong-Ki Kim in the Applied Mechanobiology Group (AMG) at Korea University for in-depth discussion of cellular and nuclear mechanobiology. This work was supported by the KU-KIST Graduate School of Converging Science and Technology Program, the National Research Foundation of Korea (NRF-2016R1C1B2015018 and NRF-2017K2A9A1A01092963), and Korea University Future Research Grant.

References

  1. 1.
    Schirmer EC, Foisner R (2007) Proteins that associate with lamins: many faces, many functions. Exp Cell Res 313:2167–2179.  https://doi.org/10.1016/j.yexcr.2007.03.012 CrossRefPubMedGoogle Scholar
  2. 2.
    Denais C, Lammerding J (2014) In: Schirmer EC, de las Heras JI (eds) Cancer biology and the nuclear envelope: recent advances may elucidate past paradoxes. Springer, New York, pp 435–470CrossRefGoogle Scholar
  3. 3.
    Rout MP, Aitchison JD, Magnasco MO, Chait BT (2003) Virtual gating and nuclear transport: the hole picture. Trends Cell Biol 13:622–628.  https://doi.org/10.1016/j.tcb.2003.10.007 CrossRefPubMedGoogle Scholar
  4. 4.
    Mackay DR, Makise M, Ullman KS (2010) Defects in nuclear pore assembly lead to activation of an Aurora B-mediated abscission checkpoint. J Cell Biol 191:923–931.  https://doi.org/10.1083/jcb.201007124 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Smythe C, Jenkins HE, Hutchison CJ (2000) Incorporation of the nuclear pore basket protein nup153 into nuclear pore structures is dependent upon lamina assembly: evidence from cell-free extracts of Xenopus eggs. EMBO J 19:3918–3931.  https://doi.org/10.1093/emboj/19.15.3918 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Zhou L, Pante N (2010) The nucleoporin Nup153 maintains nuclear envelope architecture and is required for cell migration in tumor cells. FEBS Lett 584:3013–3020.  https://doi.org/10.1016/j.febslet.2010.05.038 CrossRefPubMedGoogle Scholar
  7. 7.
    Foisner R, Gerace L (1993) Integral membrane proteins of the nuclear envelope interact with lamins and chromosomes, and binding is modulated by mitotic phosphorylation. Cell 73:1267–1279.  https://doi.org/10.1016/0092-8674(93)90355-T CrossRefPubMedGoogle Scholar
  8. 8.
    Zwerger M, Ho CY, Lammerding J (2011) Nuclear mechanics in disease. Annu Rev Biomed Eng 13:397–428.  https://doi.org/10.1146/annurev-bioeng-071910-124736 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Webster M, Witkin KL, Cohen-Fix O (2009) Sizing up the nucleus: nuclear shape, size and nuclear-envelope assembly. J Cell Sci 122: 1477–1486.  https://doi.org/10.1242/jcs.037333 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Gaines P et al (2008) Mouse neutrophils lacking lamin B-receptor expression exhibit aberrant development and lack critical functional responses. Exp Hematol 36:965–976.  https://doi.org/10.1016/j.exphem.2008.04.006 CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Brandt A et al (2006) Developmental control of nuclear size and shape by Kugelkern and Kurzkern. Curr Biol 16:543–552.  https://doi.org/10.1016/j.cub.2006.01.051 CrossRefPubMedGoogle Scholar
  12. 12.
    Pilot F, Philippe J-M, Lemmers C, Chauvin J-P, Lecuit T (2006) Developmental control of nuclear morphogenesis and anchoring by Charleston, identified in a functional genomic screen of Drosophila cellularisation. Development 133: 711–723.  https://doi.org/10.1242/dev.02251 CrossRefPubMedGoogle Scholar
  13. 13.
    Yen A, Pardee A (1979) Role of nuclear size in cell growth initiation. Science 204:1315–1317.  https://doi.org/10.1126/science.451539 CrossRefPubMedGoogle Scholar
  14. 14.
    Finan JD, Chalut KJ, Wax A, Guilak F (2009) Nonlinear osmotic properties of the cell nucleus. Ann Biomed Eng 37:477–491.  https://doi.org/10.1007/s10439-008-9618-5 CrossRefPubMedGoogle Scholar
  15. 15.
    Aebi U, Cohn J, Buhle L, Gerace L (1986) The nuclear lamina is a meshwork of intermediate-type filaments. Nature 323:560–564.  https://doi.org/10.1038/323560a0 CrossRefPubMedGoogle Scholar
  16. 16.
    Herrmann H, Aebi U (2004) Intermediate filaments: molecular structure, assembly mechanism, and integration into functionally distinct intracellular Scaffolds. Annu Rev Biochem 73:749–789.  https://doi.org/10.1146/annurev.biochem.73.011303.073823 CrossRefPubMedGoogle Scholar
  17. 17.
    Gruenbaum Y et al (2003) The nuclear lamina and its functions in the nucleus. Int Rev Cytol 226:1–62CrossRefGoogle Scholar
  18. 18.
    Stuurman N, Heins S, Aebi U (1998) Nuclear lamins: their structure, assembly, and interactions. J Struct Biol 122:42–66.  https://doi.org/10.1006/jsbi.1998.3987 CrossRefPubMedGoogle Scholar
  19. 19.
    Ellenberg J, Lippincott-Schwartz J (1999) Dynamics and mobility of nuclear envelope proteins in interphase and mitotic cells revealed by green fluorescent protein chimeras. Methods 19:362–372.  https://doi.org/10.1006/meth.1999.0872 CrossRefPubMedGoogle Scholar
  20. 20.
    Dahl KN, Engler AJ, Pajerowski JD, Discher DE (2005) Power-law rheology of isolated nuclei with deformation mapping of nuclear substructures. Biophys J 89:2855–2864.  https://doi.org/10.1529/biophysj.105.062554 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Dahl KN, Kahn SM, Wilson KL, Discher DE (2004) The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J Cell Sci 117: 4779–4786CrossRefGoogle Scholar
  22. 22.
    Newport JW, Wilson KL, Dunphy WG (1990) A lamin-independent pathway for nuclear envelope assembly. J Cell Biol 111:2247–2259.  https://doi.org/10.1083/jcb.111.6.2247 CrossRefPubMedGoogle Scholar
  23. 23.
    Lammerding J et al (2004) Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J Clin Invest 113:370–378CrossRefGoogle Scholar
  24. 24.
    Lammerding J et al (2006) Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 281:25768–25780.  https://doi.org/10.1074/jbc.M513511200 CrossRefPubMedGoogle Scholar
  25. 25.
    Kim DH et al (2012) Actin cap associated focal adhesions and their distinct role in cellular mechanosensing. Sci Rep 2:555.  https://doi.org/10.1038/srep00555 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Kouzarides T (2007) Chromatin modifications and their function. Cell 128:693–705CrossRefGoogle Scholar
  27. 27.
    Jenuwein T, Allis CD (2001) Translating the histone code. Science 293:1074–1080CrossRefGoogle Scholar
  28. 28.
    Dahl KN, Ribeiro AJ, Lammerding J (2008) Nuclear shape, mechanics, and mechanotransduction. Circ Res 102:1307–1318.  https://doi.org/10.1161/circresaha.108.173989 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Schreiner SM, Koo PK, Zhao Y, Mochrie SGJ, King MC (2015) The tethering of chromatin to the nuclear envelope supports nuclear mechanics. Nat Commun 6:7159.  https://doi.org/10.1038/ncomms8159. https://www.nature.com/articles/ncomms8159#supplementary-information CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Pajerowski JD, Dahl KN, Zhong FL, Sammak PJ, Discher DE (2007) Physical plasticity of the nucleus in stem cell differentiation. Proc Natl Acad Sci U S A 104:15619–15624.  https://doi.org/10.1073/pnas.0702576104 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Melling M et al (2001) Atomic force microscopy imaging of the human trigeminal ganglion. NeuroImage 14:1348–1352CrossRefGoogle Scholar
  32. 32.
    Raška I, Shaw PJ, Cmarko D (2006) Structure and function of the nucleolus in the spotlight. Curr Opin Cell Biol 18:325–334CrossRefGoogle Scholar
  33. 33.
    Andrade L, Tan EM, Chan E (1993) Immunocytochemical analysis of the coiled body in the cell cycle and during cell proliferation. Proc Natl Acad Sci 90:1947–1951CrossRefGoogle Scholar
  34. 34.
    Sahin U et al (2014) Oxidative stress–induced assembly of PML nuclear bodies controls sumoylation of partner proteins. J Cell Biol 204:931–945.  https://doi.org/10.1083/jcb.201305148 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Jockusch BM, Schoenenberger C-A, Stetefeld J, Aebi U (2006) Tracking down the different forms of nuclear actin. Trends Cell Biol 16: 391–396CrossRefGoogle Scholar
  36. 36.
    Visa N, Percipalle P (2010) Nuclear functions of actin. Cold Spring Harb Perspect Biol 2:a000620CrossRefGoogle Scholar
  37. 37.
    Hofmann WA, Johnson T, Klapczynski M, Fan J-L, De Lanerolle P (2006) From transcription to transport: emerging roles for nuclear myosin I this paper is one of a selection of papers published in this special issue, entitled 27th international west coast chromatin and chromosome conference, and has undergone the Journal’s usual peer review process. Biochem Cell Biol 84:418–426CrossRefGoogle Scholar
  38. 38.
    Young KG, Kothary R (2005) Spectrin repeat proteins in the nucleus. BioEssays 27:144–152CrossRefGoogle Scholar
  39. 39.
    Swift J et al (2013) Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science 341:1240104.  https://doi.org/10.1126/science.1240104 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Panorchan P, Schafer BW, Wirtz D, Tseng Y (2004) Nuclear envelope breakdown requires overcoming the mechanical integrity of the nuclear lamina. J Biol Chem 279:43462–43467CrossRefGoogle Scholar
  41. 41.
    Shin JW et al (2013) Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells. Proc Natl Acad Sci U S A 110:18892–18897.  https://doi.org/10.1073/pnas.1304996110 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Lammerding J, Dahl KN, Discher DE, Kamm RD (2007) Nuclear mechanics and methods. Methods Cell Biol 83:269–294.  https://doi.org/10.1016/s0091-679x(07)83011-1 CrossRefPubMedGoogle Scholar
  43. 43.
    Lammerding J (2011) Mechanics of the nucleus. Compr Physiol 1:783–807.  https://doi.org/10.1002/cphy.c100038 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Maniotis AJ, Chen CS, Ingber DE (1997) Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A 94:849–854CrossRefGoogle Scholar
  45. 45.
    Crisp M et al (2006) Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol 172:41–53.  https://doi.org/10.1083/jcb.200509124 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Luke Y et al (2008) Nesprin-2 Giant (NUANCE) maintains nuclear envelope architecture and composition in skin. J Cell Sci 121:1887–1898.  https://doi.org/10.1242/jcs.019075 CrossRefPubMedGoogle Scholar
  47. 47.
    Wilhelmsen K et al (2005) Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J Cell Biol 171:799–810.  https://doi.org/10.1083/jcb.200506083 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Belaadi N, Aureille J, Guilluy C (2016) Under pressure: mechanical stress management in the nucleus. Cells 5. doi: https://doi.org/10.3390/cells5020027 CrossRefGoogle Scholar
  49. 49.
    Razafsky D, Wirtz D, Hodzic D (2014) Nuclear envelope in nuclear positioning and cell migration. Adv Exp Med Biol 773:471–490.  https://doi.org/10.1007/978-1-4899-8032-8_21 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Salpingidou G, Smertenko A, Hausmanowa-Petrucewicz I, Hussey PJ, Hutchison CJ (2007) A novel role for the nuclear membrane protein emerin in association of the centrosome to the outer nuclear membrane. J Cell Biol 178:897–904.  https://doi.org/10.1083/jcb.200702026 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Kaminski A, Fedorchak GR, Lammerding J (2014) The cellular mastermind(?)-mechanotransduction and the nucleus. Prog Mol Biol Transl Sci 126:157–203.  https://doi.org/10.1016/b978-0-12-394624-9.00007-5 CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Engler AJ, Sen S, Sweeney HL, Discher DE (2006) Matrix elasticity directs stem cell lineage specification. Cell 126:677–689CrossRefGoogle Scholar
  53. 53.
    Lo CM, Wang HB, Dembo M, Wang YL (2000) Cell movement is guided by the rigidity of the substrate. Biophys J 79:144–152.  https://doi.org/10.1016/s0006-3495(00)76279-5 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Assoian RK, Klein EA (2008) Growth control by intracellular tension and extracellular stiffness. Trends Cell Biol 18:347–352.  https://doi.org/10.1016/j.tcb.2008.05.002 CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Deguchi S, Maeda K, Ohashi T, Sato M (2005) Flow-induced hardening of endothelial nucleus as an intracellular stress-bearing organelle. J Biomech 38:1751–1759.  https://doi.org/10.1016/j.jbiomech.2005.06.003 CrossRefPubMedGoogle Scholar
  56. 56.
    Guilak F (1995) Compression-induced changes in the shape and volume of the chondrocyte nucleus. J Biomech 28:1529–1541CrossRefGoogle Scholar
  57. 57.
    Broers JL et al (2004) Decreased mechanical stiffness in LMNA−/− cells is caused by defective nucleo-cytoskeletal integrity: implications for the development of laminopathies. Hum Mol Genet 13:2567–2580CrossRefGoogle Scholar
  58. 58.
    Lovett DB, Shekhar N, Nickerson JA, Roux KJ, Lele TP (2013) Modulation of nuclear shape by substrate rigidity. Cell Mol Bioeng 6:230–238.  https://doi.org/10.1007/s12195-013-0270-2 CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Thery M et al (2006) Anisotropy of cell adhesive microenvironment governs cell internal organization and orientation of polarity. Proc Natl Acad Sci U S A 103:19771–19776.  https://doi.org/10.1073/pnas.0609267103 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Emerson LJ et al (2009) Defects in cell spreading and ERK1/2 activation in fibroblasts with lamin A/C mutations. Biochim Biophys Acta 1792:810–821.  https://doi.org/10.1016/j.bbadis.2009.05.007 CrossRefPubMedGoogle Scholar
  61. 61.
    Halder G, Dupont S, Piccolo S (2012) Transduction of mechanical and cytoskeletal cues by YAP and TAZ. Nat Rev Mol Cell Biol 13:591–600.  https://doi.org/10.1038/nrm3416 CrossRefPubMedGoogle Scholar
  62. 62.
    Ho CY, Jaalouk DE, Vartiainen MK, Lammerding J (2013) Lamin A/C and emerin regulate MKL1-SRF activity by modulating actin dynamics. Nature 497:507–511.  https://doi.org/10.1038/nature12105. http://www.nature.com/nature/journal/v497/n7450/abs/nature12105.html#supplementary-information CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Robinson JA et al (2006) Wnt/beta-catenin signaling is a normal physiological response to mechanical loading in bone. J Biol Chem 281:31720–31728.  https://doi.org/10.1074/jbc.M602308200 CrossRefPubMedGoogle Scholar
  64. 64.
    Luger K, Mäder AW, Richmond RK, Sargent DF, Richmond TJ (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–260CrossRefGoogle Scholar
  65. 65.
    Wang Y, Leung FC (2004) An evaluation of new criteria for CpG islands in the human genome as gene markers. Bioinformatics 20:1170–1177CrossRefGoogle Scholar
  66. 66.
    Suzuki MM, Bird A (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9:465–476CrossRefGoogle Scholar
  67. 67.
    Bird A (2002) DNA methylation patterns and epigenetic memory. Genes Dev 16:6–21CrossRefGoogle Scholar
  68. 68.
    Watt F, Molloy PL (1988) Cytosine methylation prevents binding to DNA of a HeLa cell transcription factor required for optimal expression of the adenovirus major late promoter. Genes Dev 2: 1136–1143CrossRefGoogle Scholar
  69. 69.
    Kim GD, Ni J, Kelesoglu N, Roberts RJ, Pradhan S (2002) Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases. EMBO J 21: 4183–4195CrossRefGoogle Scholar
  70. 70.
    Hebbes TR, Thorne AW, Crane-Robinson C (1988) A direct link between core histone acetylation and transcriptionally active chromatin. EMBO J 7:1395CrossRefGoogle Scholar
  71. 71.
    Liang G et al (2004) Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci U S A 101:7357–7362CrossRefGoogle Scholar
  72. 72.
    Haberland M, Montgomery RL, Olson EN (2009) The many roles of histone deacetylases in development and physiology: implications for disease and therapy. Nat Rev Genet 10:32–42CrossRefGoogle Scholar
  73. 73.
    Shi Y (2007) Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet 8:829–833CrossRefGoogle Scholar
  74. 74.
    Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10:295–304CrossRefGoogle Scholar
  75. 75.
    Nan X et al (1998) Transcriptional repression by the methyl-CpG-binding protein MeCP2 involves a histone deacetylase complex. Nature 393:386–389CrossRefGoogle Scholar
  76. 76.
    Jiang C, Pugh BF (2009) Nucleosome positioning and gene regulation: advances through genomics. Nat Rev Genet 10:161–172CrossRefGoogle Scholar
  77. 77.
    Ozsolak F, Song JS, Liu XS, Fisher DE (2007) High-throughput mapping of the chromatin structure of human promoters. Nat Biotechnol 25:244–248.  https://doi.org/10.1038/nbt1279 CrossRefPubMedGoogle Scholar
  78. 78.
    Jin C, Felsenfeld G (2007) Nucleosome stability mediated by histone variants H3. 3 and H2A. Z. Genes Dev 21:1519–1529CrossRefGoogle Scholar
  79. 79.
    Zlatanova J, Thakar A (2008) H2A. Z: view from the top. Structure 16:166–179CrossRefGoogle Scholar
  80. 80.
    Svotelis A, Gevry N, Gaudreau L (2009) Regulation of gene expression and cellular proliferation by histone H2A. Z this paper is one of a selection of papers published in this special issue, entitled CSBMCB’s 51st annual meeting–epigenetics and chromatin dynamics, and has undergone the Journal’s usual peer review process. Biochem Cell Biol 87:179–188CrossRefGoogle Scholar
  81. 81.
    Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297CrossRefGoogle Scholar
  82. 82.
    He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531CrossRefGoogle Scholar
  83. 83.
    Zhang B, Pan X, Cobb GP, Anderson T (2007) A. microRNAs as oncogenes and tumor suppressors. Dev Biol 302:1–12.  https://doi.org/10.1016/j.ydbio.2006.08.028 CrossRefPubMedGoogle Scholar
  84. 84.
    Friedman JM et al (2009) The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res 69:2623–2629.  https://doi.org/10.1158/0008-5472.can-08-3114 CrossRefPubMedGoogle Scholar
  85. 85.
    Fabbri M et al (2007) MicroRNA-29 family reverts aberrant methylation in lung cancer by targeting DNA methyltransferases 3A and 3B. Proc Natl Acad Sci 104:15805–15810CrossRefGoogle Scholar
  86. 86.
    Gundersen GG, Worman HJ (2013) Nuclear positioning. Cell 152:1376–1389.  https://doi.org/10.1016/j.cell.2013.02.031 CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Doyle AD, Wang FW, Matsumoto K, Yamada KM (2009) One-dimensional topography underlies three-dimensional fibrillar cell migration. J Cell Biol 184:481–490.  https://doi.org/10.1083/jcb.200810041 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Palazzo AF et al (2001) Cdc42, dynein, and dynactin regulate MTOC reorientation independent of Rho-regulated microtubule stabilization. Curr Biol 11:1536–1541CrossRefGoogle Scholar
  89. 89.
    Kutscheidt S et al (2014) FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement. Nat Cell Biol 16:708–715.  https://doi.org/10.1038/ncb2981 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Kim D-H, Cho S, Wirtz D (2014) Tight coupling between nucleus and cell migration through the perinuclear actin cap. J Cell Sci 127:2528–2541.  https://doi.org/10.1242/jcs.144345 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Chancellor TJ, Lee J, Thodeti CK, Lele T (2010) Actomyosin tension exerted on the nucleus through Nesprin-1 connections influences endothelial cell adhesion, migration, and cyclic strain-induced reorientation. Biophys J 99:115–123.  https://doi.org/10.1016/j.bpj.2010.04.011 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Zink D, H Fischer A, Nickerson J (2004) Nuclear structure in cancer cells. Nat Rev Cancer 4:677–687CrossRefGoogle Scholar
  93. 93.
    Wolf K et al (2013) Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol 201:1069–1084CrossRefGoogle Scholar
  94. 94.
    Vargas JD, Hatch EM, Anderson DJ, Hetzer MW (2012) Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus 3:88–100CrossRefGoogle Scholar
  95. 95.
    Leman ES, Getzenberg RH (2002) Nuclear matrix proteins as biomarkers in prostate cancer. J Cell Biochem 86:213–223CrossRefGoogle Scholar
  96. 96.
    Lever E, Sheer D (2010) The role of nuclear organization in cancer. J Pathol 220:114–125PubMedGoogle Scholar
  97. 97.
    Coradeghini R et al (2006) Differential expression of nuclear lamins in normal and cancerous prostate tissues. Oncol Rep 15:609–614PubMedGoogle Scholar
  98. 98.
    Shen F et al (2011) Nuclear protein isoforms: implications for cancer diagnosis and therapy. J Cell Biochem 112:756–760.  https://doi.org/10.1002/jcb.23002 CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Willis ND et al (2008) Lamin A/C is a risk biomarker in colorectal cancer. PLoS One 3:e2988CrossRefGoogle Scholar
  100. 100.
    Helfand BT et al (2012) Chromosomal regions associated with prostate cancer risk localize to lamin B-deficient microdomains and exhibit reduced gene transcription. J Pathol 226:735–745.  https://doi.org/10.1002/path.3033 CrossRefPubMedGoogle Scholar
  101. 101.
    Capo-chichi CD, Cai KQ, Testa JR, Godwin AK, Xu XX (2009) Loss of GATA6 leads to nuclear deformation and aneuploidy in ovarian cancer. Mol Cell Biol 29:4766–4777.  https://doi.org/10.1128/mcb.00087-09 CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Somech R et al (2007) Enhanced expression of the nuclear envelope LAP2 transcriptional repressors in normal and malignant activated lymphocytes. Ann Hematol 86:393–401.  https://doi.org/10.1007/s00277-007-0275-9 CrossRefPubMedGoogle Scholar
  103. 103.
    Sjöblom T et al (2006) The consensus coding sequences of human breast and colorectal cancers. Science 314:268–274.  https://doi.org/10.1126/science.1133427 CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Takahashi N et al (2008) Tumor marker nucleoporin 88 kDa regulates nucleocytoplasmic transport of NF-κB. Biochem Biophys Res Commun 374:424–430.  https://doi.org/10.1016/j.bbrc.2008.06.128 CrossRefPubMedGoogle Scholar
  105. 105.
    Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31:27–36.  https://doi.org/10.1093/carcin/bgp220 CrossRefPubMedGoogle Scholar
  106. 106.
    Rodriguez J et al (2006) Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res 66:8462–9468CrossRefGoogle Scholar
  107. 107.
    Lee TS et al (2006) DNA hypomethylation of CAGE promotors in squamous cell carcinoma of uterine cervix. Ann N Y Acad Sci 1091:218–224.  https://doi.org/10.1196/annals.1378.068 CrossRefPubMedGoogle Scholar
  108. 108.
    Takano Y, Kato Y, Masuda M, Ohshima Y, Okayasu I (1999) Cyclin D2, but not cyclin D1, overexpression closely correlates with gastric cancer progression and prognosis. J Pathol 189:194–200.  https://doi.org/10.1002/(sici)1096-9896(199910)189:2<194::aid-path426>3.0.co;2-p CrossRefPubMedGoogle Scholar
  109. 109.
    Neupane D, Korc M (2008) 14-3-3sigma modulates pancreatic cancer cell survival and invasiveness. Clin Cancer Res 14:7614–7623.  https://doi.org/10.1158/1078-0432.ccr-08-1366 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Hedenfalk I et al (2001) Gene-expression profiles in hereditary breast cancer. N Engl J Med 344:539–548.  https://doi.org/10.1056/nejm200102223440801 CrossRefPubMedGoogle Scholar
  111. 111.
    Halkidou K et al (2004) Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate 59:177–189CrossRefGoogle Scholar
  112. 112.
    Fraga MF et al (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37: 391–400CrossRefGoogle Scholar
  113. 113.
    Yang XJ (2004) The diverse superfamily of lysine acetyltransferases and their roles in leukemia and other diseases. Nucleic Acids Res 32: 959–976CrossRefGoogle Scholar
  114. 114.
    Nguyen CT et al (2002) Histone H3-lysine 9 methylation is associated with aberrant gene silencing in cancer cells and is rapidly reversed by 5-aza-2′-deoxycytidine. Cancer Res 62:6456–6461PubMedGoogle Scholar
  115. 115.
    Valk-Lingbeek ME, Bruggeman SW, van Lohuizen M (2004) Stem cells and cancer: the polycomb connection. Cell 118:409–418CrossRefGoogle Scholar
  116. 116.
    Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692.  https://doi.org/10.1016/j.cell.2007.01.029 CrossRefPubMedPubMedCentralGoogle Scholar
  117. 117.
    Morey L et al (2008) MBD3, a component of the NuRD complex, facilitates chromatin alteration and deposition of epigenetic marks. Mol Cell Biol 28:5912–5923.  https://doi.org/10.1128/mcb.00467-08 CrossRefPubMedPubMedCentralGoogle Scholar
  118. 118.
    Svotelis A, Gevry N, Gaudreau L (2009) Regulation of gene expression and cellular proliferation by histone H2A.Z. Biochem Cell Biol 87:179–188.  https://doi.org/10.1139/o08-138 CrossRefPubMedGoogle Scholar
  119. 119.
    Roush S, Slack FJ (2008) The let-7 family of microRNAs. Trends Cell Biol 18:505–516.  https://doi.org/10.1016/j.tcb.2008.07.007 CrossRefPubMedGoogle Scholar
  120. 120.
    Iorio MV et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070.  https://doi.org/10.1158/0008-5472.can-05-1783 CrossRefPubMedGoogle Scholar
  121. 121.
    Takamizawa J et al (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res 64:3753–3756.  https://doi.org/10.1158/0008-5472.can-04-0637 CrossRefPubMedGoogle Scholar
  122. 122.
    Hayashita Y et al (2005) A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res 65:9628–9632.  https://doi.org/10.1158/0008-5472.can-05-2352 CrossRefPubMedGoogle Scholar
  123. 123.
    Michael MZ, SM OC, van Holst Pellekaan NG, Young GP, James RJ (2003) Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1:882–891PubMedGoogle Scholar
  124. 124.
    Gomes ER, Jani S, Gundersen GG (2005) Nuclear movement regulated by Cdc42, MRCK, myosin, and actin flow establishes MTOC polarization in migrating cells. Cell 121:451–463.  https://doi.org/10.1016/j.cell.2005.02.022 CrossRefPubMedGoogle Scholar
  125. 125.
    Hawkins RJ et al (2009) Pushing off the walls: a mechanism of cell motility in confinement. Phys Rev Lett 102:058103.  https://doi.org/10.1103/PhysRevLett.102.058103 CrossRefPubMedGoogle Scholar
  126. 126.
    Harada T et al (2014) Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol 204:669–682.  https://doi.org/10.1083/jcb.201308029 CrossRefPubMedPubMedCentralGoogle Scholar
  127. 127.
    Beadle C et al (2008) The role of myosin II in glioma invasion of the brain. Mol Biol Cell 19:3357–3368CrossRefGoogle Scholar
  128. 128.
    Osorio DS, Gomes ER (2014) In: Schirmer EC, de las Heras JI (eds) Cancer biology and the nuclear envelope: recent advances may elucidate past paradoxes. Springer, New York, pp 505–520CrossRefGoogle Scholar
  129. 129.
    Friedl P, Wolf K, Lammerding J (2011) Nuclear mechanics during cell migration. Curr Opin Cell Biol 23:55–64CrossRefGoogle Scholar
  130. 130.
    Razafsky D, Wirtz D, Hodzic D (2014) Cancer biology and the nuclear envelope. Springer, New York, pp 471–490CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Korea UniversitySeoulKorea
  2. 2.The Johns Hopkins UniversityBaltimoreUSA

Personalised recommendations