Advertisement

The Nuclear Envelope and Cancer: A Diagnostic Perspective and Historical Overview

Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 773)

Abstract

Cancer has been diagnosed for millennia, but its cellular nature only began to be understood in the mid-nineteenth century when advances in microscopy allowed detailed specimen observations. It was soon noted that cancer cells often possessed nuclei that were altered in size and/or shape. This became an important criterion for cancer diagnosis that continues to be used today. The mechanisms linking nuclear abnormalities and cancer only started to be understood in the second half of the twentieth century, with the discovery of nuclear lamina composition differences in cancer cells compared to normal cells. The nuclear envelope, rather than providing a mere physical barrier between the genetic material in the nucleus and the cytoplasm, is a very important functional hub for many cellular processes. In this review we give an overview of the links between cancer biology and nuclear envelope, from the early days of microscopy until the present day’s understanding of some of the molecular mechanisms behind those links.

Keywords

Cytology Diagnostics Karyoplasmic ratio NETs NPC Nuclear lamina Nuclear size 

Abbreviations

H&E

Hematoxylin and eosin

NET

Nuclear envelope transmembrane protein

NPC

Nuclear pore complex

Notes

Acknowledgments

Work in the Schirmer lab is supported by Wellcome Trust Senior Research Fellowship 095209.

References

  1. 1.
    David AR, Zimmerman MR (2010) Cancer: an old disease, a new disease or something in between? Nat Rev Cancer 10(10):728–733. doi: 10.1038/Nrc2914 PubMedCrossRefGoogle Scholar
  2. 2.
    Jay V (2002) Antony van Leeuwenhoek. Arch Pathol Lab Med 126(6):658–659Google Scholar
  3. 3.
    Lister JJ (1830) On some properties in achromatic object-glasses applicable to the improvement of the microscope. Phil Trans R Soc Lond 120:187–200CrossRefGoogle Scholar
  4. 4.
    Boveri T (2008) Concerning the origin of malignant tumours by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci 121(Suppl 1):1–84. doi: 10.1242/jcs.025742 PubMedCrossRefGoogle Scholar
  5. 5.
    Müller J (1838) Über den feineren Bau und die Formen der krankhaften Geschwülste. (On the nature and structural characteristics of cancer, and of those morbid growths which may be confounded with it) (trans: West C). G. Reimer, BerlinGoogle Scholar
  6. 6.
    Donne A (1844) Cours de Microscopie Complementaire des Etudes Medicales. Chez J.B Bailliere, ParisGoogle Scholar
  7. 7.
    Bennett JH (1845) Case 2, case of hypertrophy of the spleen and liver, in which death took place from suppuration of the blood. Edinb Med Surg J 64:413–423Google Scholar
  8. 8.
    Walshe WH (1846) The nature and treatment of cancer. Taylor and Walton, LondonGoogle Scholar
  9. 9.
    Vogel J (1847) The pathological anatomy of the human body. (The pathological anatomy of the human body) (trans: Day GEC, L.M.). H. Bailliere, LondonGoogle Scholar
  10. 10.
    Bennett JH (1849) On cancerous and cancroid growths. Sutherland & Knox, EdinburghGoogle Scholar
  11. 11.
    Lebert H (1851) Traité Pratique des Maladies Cancéreuses et des Affections Curables Confondues aver le Cancer. Bailliere, ParisGoogle Scholar
  12. 12.
    Wilson EB (1925) The karyoplasmic ratio. In: Wilson EB (ed) The cell in development and heredity, 3rd edn. The Macmillan Company, New York, pp 727–733Google Scholar
  13. 13.
    Lebert H (1845) Physiologie pathologique ou récherches clinique, experimentales et microscopiques. Bailliere, ParisGoogle Scholar
  14. 14.
    Beale LS (1854) The microscope and its application to clinical medicine. Highley, LondonGoogle Scholar
  15. 15.
    Beale LS (1860) Examination of sputum from a case of cancer of the pharynx and the adjacent parts. Arch Med Lond 2:44Google Scholar
  16. 16.
    Naylor B (2000) The century for cytopathology. Acta Cytol 44(5):709–725PubMedCrossRefGoogle Scholar
  17. 17.
    Virchow R (1863) Die Krankhaften Geschwülste, vol 1. Hirschwald, BerlinGoogle Scholar
  18. 18.
    Virchow R (1865) Die Krankhaften Geschwülste, vol 2. Hirschwald, BerlinGoogle Scholar
  19. 19.
    Virchow R (1865) Die Krankhaften Geschwülste, vol 3. Hirschwald, BerlinGoogle Scholar
  20. 20.
    Virchow R (1858) Die Cellularpathologie in ihrer Begrundung auf physiologische und pathologische Gewebelehre. (Cellular pathology as based upon physiological and pathological histology) (trans: Chance F). Hirschwald, BerlinGoogle Scholar
  21. 21.
    Wissowzky A (1876) Ueber das Eosin als reagenz auf Hämoglobin und die Bildung von Blutgefässen und Blutkörperchen bei Säugetier und Hühnerembryonen. Arch Mikrosk Anat 13:479–496CrossRefGoogle Scholar
  22. 22.
    Papanicolaou GN (1928) New cancer diagnosis. Proceedings of the 3rd race betterment conference. RBF, Battle Creek, MIGoogle Scholar
  23. 23.
    Papanicolaou GN (1942) A New Procedure for Staining Vaginal Smears. Science 95(2469):438–439. doi: 10.1126/science.95.2469.438 PubMedCrossRefGoogle Scholar
  24. 24.
    Papanicolaou GN, Traut HF (1941) The diagnostic value of vaginal smears in carcinoma of the uterus. Am J Obstet Gynecol 42:193–206Google Scholar
  25. 25.
    Traut HF, Papanicolaou GN (1943) Cancer of the uterus: the vaginal smear in its diagnosis. Cal West Med 59(2):121–122PubMedCentralPubMedGoogle Scholar
  26. 26.
    Fu YS, Reagan JW, Benington JL (1989) Pathology of the uterine cervix, vagina, and vulva. W.B. Saunders, PhiladelphiaGoogle Scholar
  27. 27.
    Morrison LF, Hopp ES, Wu R (1949) Diagnosis of malignancy of the nasopharynx; cytological studies by the smear technic. Ann Otol Rhinol Laryngol 58(1):18–32PubMedGoogle Scholar
  28. 28.
    Montgomery PW, Vonhaam E (1951) A study of the exfoliative cytology in patients with carcinoma of the oral mucosa. J Dent Res 30(3):308–313. doi: 10.1177/00220345510300030201 PubMedCrossRefGoogle Scholar
  29. 29.
    Patten SF, Reagan JW, Obenauf M (1959) An analytical approach to the diagnosis of endometrial adenocarcinoma in cytologic material. Trans Intersoc Cytol Council 7:153–156Google Scholar
  30. 30.
    Reagan JW, Patten SF (1961) An analytical study of the cellular changes in carcinoma in situ, squamous cell cancer and adenocarcinoma of the uterine cervix. Clin Obstet Gynecol 4:1047–1127CrossRefGoogle Scholar
  31. 31.
    Wied GL, Meier P, Clark LM (1964) An electronic data processing program for cytologic screening projects for uterine carcinoma. Acta Cytol 8(6):385–397PubMedGoogle Scholar
  32. 32.
    Wied GL, Messina AM, Manglano JI, Meier P, Blough RR (1964) Fluorospectrophotometric analyses of endometrial and endocervical epithelial cells. Acta Cytol 8(6):408–415PubMedGoogle Scholar
  33. 33.
    Wied GL, Bahr GF, Oldfield DG, Bartels PH (1968) Computer-assisted identification of cells from uterine adenocarcinoma. A clinical feasibility study with Ticas. 1. Measurements at wavelength 530 Nm. Acta Cytol 12(5):357–370PubMedGoogle Scholar
  34. 34.
    Bartels PH, Wied GL (1997) Automated screening for cervical cancer: Diagnostic decision procedures. Acta Cytol 41(1):6–10PubMedGoogle Scholar
  35. 35.
    Bartels PH, Bahr GF, Calhoun DW, Wied GL (1970) Cell recognition by neighborhood grouping techniques in Ticas. Acta Cytol 14(6):313–324PubMedGoogle Scholar
  36. 36.
    Abdalla FB, Markus R, Buhmeida A, Boder J, Syrjanen K, Collan Y (2012) Estrogen receptor, progesterone receptor, and nuclear size features in female breast cancer in Libya: correlation with clinical features and survival. Anticancer Res 32(8):3485–3493PubMedGoogle Scholar
  37. 37.
    Nandakumar V, Kelbauskas L, Hernandez KF, Lintecum KM, Senechal P, Bussey KJ, Davies PC, Johnson RH, Meldrum DR (2012) Isotropic 3D nuclear morphometry of normal, fibrocystic and malignant breast epithelial cells reveals new structural alterations. PLoS One 7(1):e29230. doi: 10.1371/journal.pone.0029230 PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Tan PH, Goh BB, Chiang G, Bay BH (2001) Correlation of nuclear morphometry with pathologic parameters in ductal carcinoma in situ of the breast. Mod Pathol 14(10):937–941. doi: 10.1038/modpathol.3880415 PubMedCrossRefGoogle Scholar
  39. 39.
    Veta M, Kornegoor R, Huisman A, Verschuur-Maes AH, Viergever MA, Pluim JP, van Diest PJ (2012) Prognostic value of automatically extracted nuclear morphometric features in whole slide images of male breast cancer. Mod Pathol 25(12):1559–1565. doi: 10.1038/modpathol.2012.126 PubMedCrossRefGoogle Scholar
  40. 40.
    Saad RS, Kanbour-Shakir A, Lu E, Modery J, Kanbour A (2006) Cytomorphologic analysis and histological correlation of high-grade squamous intraepithelial lesions in postmenopausal women. Diagn Cytopathol 34(7):467–471. doi: 10.1002/dc.20475 PubMedCrossRefGoogle Scholar
  41. 41.
    Slater DN, Rice S, Stewart R, Melling SE, Hewer EM, Smith JH (2005) Proposed Sheffield quantitative criteria in cervical cytology to assist the grading of squamous cell dyskaryosis, as the British Society for Clinical Cytology definitions require amendment. Cytopathology 16(4):179–192. doi: 10.1111/j.1365-2303.2005.00271.x PubMedCrossRefGoogle Scholar
  42. 42.
    Giorgadze T, Kanhere R, Pang C, Ganote C, Miller LE, Tabaczka P, Brown E, Husain M (2012) Small cell carcinoma of the cervix in liquid-based Pap test: utilization of split-sample immunocytochemical and molecular analysis. Diagn Cytopathol 40(3):214–219. doi: 10.1002/dc.21542 PubMedCrossRefGoogle Scholar
  43. 43.
    Eynard HG, Soria EA, Cuestas E, Rovasio RA, Eynard AR (2009) Assessment of colorectal cancer prognosis through nuclear morphometry. J Surg Res 154(2):345–348. doi: 10.1016/j.jss.2008.06.022 PubMedCrossRefGoogle Scholar
  44. 44.
    Malhotra S, Kazlouskaya V, Andres C, Gui J, Elston D (2013) Diagnostic cellular abnormalities in neoplastic and non-neoplastic lesions of the epidermis: a morphological and statistical study. J Cutan Pathol 40(4):371–378. doi: 10.1111/cup.12090 PubMedCrossRefGoogle Scholar
  45. 45.
    Meachem MD, Burgess HJ, Davies JL, Kidney BA (2012) Utility of nuclear morphometry in the cytologic evaluation of canine cutaneous soft tissue sarcomas. J Vet Diagn Invest 24(3):525–530. doi: 10.1177/1040638712440988 PubMedCrossRefGoogle Scholar
  46. 46.
    Ikeguchi M, Oka S, Saito H, Kondo A, Tsujitani S, Maeta M, Kaibara N (1999) Computerized nuclear morphometry: a new morphologic assessment for advanced gastric adenocarcinoma. Ann Surg 229(1):55–61PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    Ladekarl M, Baek-Hansen T, Henrik-Nielsen R, Mouritzen C, Henriques U, Sorensen FB (1995) Objective malignancy grading of squamous cell carcinoma of the lung. Stereologic estimates of mean nuclear size are of prognostic value, independent of clinical stage of disease. Cancer 76(5):797–802PubMedCrossRefGoogle Scholar
  48. 48.
    Yan J, Zhuo S, Chen G, Wu X, Zhou D, Xie S, Jiang J, Ying M, Jia F, Chen J, Zhou J (2012) Preclinical study of using multiphoton microscopy to diagnose liver cancer and differentiate benign and malignant liver lesions. J Biomed Opt 17(2):026004. doi: 10.1117/1.JBO.17.2.026004 PubMedCrossRefGoogle Scholar
  49. 49.
    Na YR, Seok SH, Kim DJ, Han JH, Kim TH, Jung H, Lee BH, Park JH (2009) Isolation and characterization of spheroid cells from human malignant melanoma cell line WM-266-4. Tumour Biol 30(5–6):300–309. doi: 10.1159/000261073 PubMedCrossRefGoogle Scholar
  50. 50.
    Mossbacher U, Knollmayer S, Binder M, Steiner A, Wolff K, Pehamberger H (1996) Increased nuclear volume in metastasizing “thick” melanomas. J Invest Dermatol 106(3):437–440PubMedCrossRefGoogle Scholar
  51. 51.
    Madsen C, Schroder HD (1996) Stereological estimation of nuclear mean volume in invasive meningiomas. APMIS 104(2):103–107PubMedCrossRefGoogle Scholar
  52. 52.
    Natarajan S, Mahajan S, Boaz K, George T (2010) Prediction of lymph node metastases by preoperative nuclear morphometry in oral squamous cell carcinoma: a comparative image analysis study. Indian J Cancer 47(4):406–411. doi: 10.4103/0019-509X.73580 PubMedCrossRefGoogle Scholar
  53. 53.
    de Andrea CE, Petrilli AS, Jesus-Garcia R, Bleggi-Torres LF, Alves MT (2011) Large and round tumor nuclei in osteosarcoma: good clinical outcome. Int J Clin Exp Pathol 4(2):169–174PubMedCentralPubMedGoogle Scholar
  54. 54.
    Zeimet AG, Fiegl H, Goebel G, Kopp F, Allasia C, Reimer D, Steppan I, Mueller-Holzner E, Ehrlich M, Marth C (2011) DNA ploidy, nuclear size, proliferation index and DNA-hypomethylation in ovarian cancer. Gynecol Oncol 121(1):24–31. doi: 10.1016/j.ygyno.2010.12.332 PubMedCentralPubMedCrossRefGoogle Scholar
  55. 55.
    Taira T, Kawahara A, Yamaguchi T, Abe H, Ishida Y, Okabe Y, Naito Y, Yano H, Kage M (2012) Morphometric image analysis of pancreatic disease by ThinPrep liquid-based cytology. Diagn Cytopathol 40(11):970–975. doi: 10.1002/dc.21704 PubMedCrossRefGoogle Scholar
  56. 56.
    Rashid F, Ul Haque A (2011) Frequencies of different nuclear morphological features in prostate adenocarcinoma. Ann Diagn Pathol 15(6):414–421. doi: 10.1016/j.anndiagpath.2011.06.002 PubMedCrossRefGoogle Scholar
  57. 57.
    Shih SR, Chang YC, Li HY, Liau JY, Lee CY, Chen CM, Chang TC (2013) Preoperative prediction of papillary thyroid carcinoma prognosis with the assistance of computerized morphometry of cytology samples obtained by fine-needle aspiration: preliminary report. Head Neck 35(1):28–34. doi: 10.1002/hed.22909 PubMedCrossRefGoogle Scholar
  58. 58.
    Helander K, Hofer PA, Holmberg G (1984) Karyometric investigations on urinary bladder carcinoma, correlated to histopathological grading. Virchows Arch A Pathol Anat Histopathol 403(2):117–125PubMedCrossRefGoogle Scholar
  59. 59.
    van Velthoven R, Petein M, Oosterlinck WJ, Zandona C, Zlotta A, Van der Meijden AP, Pasteels JL, Roels H, Schulman C, Kiss R (1995) Image cytometry determination of ploidy level, proliferative activity, and nuclear size in a series of 314 transitional bladder cell carcinomas. Hum Pathol 26(1):3–11PubMedCrossRefGoogle Scholar
  60. 60.
    Fukuzawa S, Hashimura T, Sasaki M, Yamabe H, Yoshida O (1995) Nuclear morphometry for improved prediction of the prognosis of human bladder carcinoma. Cancer 76(10):1790–1796PubMedCrossRefGoogle Scholar
  61. 61.
    Suresh S (2007) Biomechanics and biophysics of cancer cells. Acta Biomater 3(4):413–438. doi: 10.1016/j.actbio.2007.04.002 PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.
    Friedl P, Wolf K, Lammerding J (2011) Nuclear mechanics during cell migration. Curr Opin Cell Biol 23(1):55–64. doi: 10.1016/j.ceb.2010.10.015 PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Wolf K, Te Lindert M, Krause M, Alexander S, Te Riet J, Willis AL, Hoffman RM, Figdor CG, Weiss SJ, Friedl P (2013) Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol 201(7):1069–1084. doi: 10.1083/jcb.201210152 PubMedCentralPubMedCrossRefGoogle Scholar
  64. 64.
    Ozaki T, Saijo M, Murakami K, Enomoto H, Taya Y, Sakiyama S (1994) Complex formation between lamin A and the retinoblastoma gene product: identification of the domain on lamin A required for its interaction. Oncogene 9(9):2649–2653PubMedGoogle Scholar
  65. 65.
    Osada S, Ohmori SY, Taira M (2003) XMAN1, an inner nuclear membrane protein, antagonizes BMP signaling by interacting with Smad1 in Xenopus embryos. Development 130(9):1783–1794PubMedCrossRefGoogle Scholar
  66. 66.
    Pan D, Estevez-Salmeron LD, Stroschein SL, Zhu X, He J, Zhou S, Luo K (2005) The integral inner nuclear membrane protein MAN1 physically interacts with the R-Smad proteins to repress signaling by the transforming growth factor-{beta} superfamily of cytokines. J Biol Chem 280(16):15992–16001. doi: 10.1074/jbc.M411234200 PubMedCrossRefGoogle Scholar
  67. 67.
    Zbarsky IB, Samarina OP, Yermolayeva LP (1964) Nuclear Proteins and Their Biosynthesis in the Tumour Cells. Acta Unio Int Contra Cancrum 20:937–940PubMedGoogle Scholar
  68. 68.
    Aaronson RP, Blobel G (1975) Isolation of nuclear pore complexes in association with a lamina. Proc Natl Acad Sci U S A 72(3):1007–1011PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Kuzmina SN, Buldyaeva TV, Akopov SB, Zbarsky IB (1984) Protein patterns of the nuclear matrix in differently proliferating and malignant cells. Mol Cell Biochem 58(1–2):183–186PubMedCrossRefGoogle Scholar
  70. 70.
    Zackroff RV, Goldman AE, Jones JC, Steinert PM, Goldman RD (1984) Isolation and characterization of keratin-like proteins from cultured cells with fibroblastic morphology. J Cell Biol 98(4):1231–1237PubMedCrossRefGoogle Scholar
  71. 71.
    McKeon FD, Kirschner MW, Caput D (1986) Homologies in both primary and secondary structure between nuclear envelope and intermediate filament proteins. Nature 319(6053):463–468. doi: 10.1038/319463a0 PubMedCrossRefGoogle Scholar
  72. 72.
    Fisher DZ, Chaudhary N, Blobel G (1986) cDNA sequencing of nuclear lamins A and C reveals primary and secondary structural homology to intermediate filament proteins. Proc Natl Acad Sci U S A 83(17):6450–6454PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Stuurman N, Heins S, Aebi U (1998) Nuclear lamins: their structure, assembly, and interactions. J Struct Biol 122(1–2):42–66. doi: 10.1006/jsbi.1998.3987 PubMedCrossRefGoogle Scholar
  74. 74.
    Janmey PA, Euteneuer U, Traub P, Schliwa M (1991) Viscoelastic properties of vimentin compared with other filamentous biopolymer networks. J Cell Biol 113(1):155–160PubMedCrossRefGoogle Scholar
  75. 75.
    Schirmer EC, Gerace L (2004) The stability of the nuclear lamina polymer changes with the composition of lamin subtypes according to their individual binding strengths. J Biol Chem 279(41):42811–42817. doi: 10.1074/jbc.M407705200 PubMedCrossRefGoogle Scholar
  76. 76.
    Lammerding J, Fong LG, Ji JY, Reue K, Stewart CL, Young SG, Lee RT (2006) Lamins A and C but not lamin B1 regulate nuclear mechanics. J Biol Chem 281(35):25768–25780. doi: 10.1074/jbc.M513511200 PubMedCrossRefGoogle Scholar
  77. 77.
    Suntharalingam M, Wente SR (2003) Peering through the pore: nuclear pore complex structure, assembly, and function. Dev Cell 4(6):775–789PubMedCrossRefGoogle Scholar
  78. 78.
    Schirmer EC, Florens L, Guan T, Yates JR 3rd, Gerace L (2003) Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301(5638):1380–1382. doi: 10.1126/science.1088176 PubMedCrossRefGoogle Scholar
  79. 79.
    Wilkie GS, Korfali N, Swanson SK, Malik P, Srsen V, Batrakou DG, Heras J, Zuleger N, Kerr AR, Florens L, Schirmer EC (2011) Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations. Mol Cell Proteomics 10(1):M110 003129. doi: 10.1074/mcp.M110.003129 PubMedCentralPubMedCrossRefGoogle Scholar
  80. 80.
    Korfali N, Wilkie GS, Swanson SK, Srsen V, Batrakou DG, Fairley EA, Malik P, Zuleger N, Goncharevich A, de Las HJ, Kelly DA, Kerr AR, Florens L, Schirmer EC (2010) The leukocyte nuclear envelope proteome varies with cell activation and contains novel transmembrane proteins that affect genome architecture. Mol Cell Proteomics 9(12):2571–2585. doi: 10.1074/mcp.M110.002915 PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Korfali N, Wilkie GS, Swanson SK, Srsen V, de Las HJ, Batrakou DG, Malik P, Zuleger N, Kerr AR, Florens L, Schirmer EC (2012) The nuclear envelope proteome differs notably between tissues. Nucleus 3(6):552–564. doi: 10.4161/nucl.22257 PubMedCentralPubMedCrossRefGoogle Scholar
  82. 82.
    de Las Heras JI, Batrakou DG, Schirmer EC (2013) Cancer biology and the nuclear envelope: a convoluted relationship. Semin Cancer Biol 23(2):125–137. doi: 10.1016/j.semcancer.2012.01.008 PubMedCrossRefGoogle Scholar
  83. 83.
    Chow KH, Factor RE, Ullman KS (2012) The nuclear envelope environment and its cancer connections. Nat Rev Cancer 12(3):196–209. doi: 10.1038/nrc3219 PubMedGoogle Scholar
  84. 84.
    Malik P, Korfali N, Srsen V, Lazou V, Batrakou DG, Zuleger N, Kavanagh DM, Wilkie GS, Goldberg MW, Schirmer EC (2010) Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope. Cell Mol Life Sci 67(8):1353–1369. doi: 10.1007/s00018-010-0257-2 PubMedCentralPubMedCrossRefGoogle Scholar
  85. 85.
    Brachner A, Reipert S, Foisner R, Gotzmann J (2005) LEM2 is a novel MAN1-related inner nuclear membrane protein associated with A-type lamins. J Cell Sci 118(Pt 24):5797–5810. doi: 10.1242/jcs.02701 PubMedCrossRefGoogle Scholar
  86. 86.
    Chen IH, Huber M, Guan T, Bubeck A, Gerace L (2006) Nuclear envelope transmembrane proteins (NETs) that are up-regulated during myogenesis. BMC Cell Biol 7:38. doi: 10.1186/1471-2121-7-38 PubMedCentralPubMedCrossRefGoogle Scholar
  87. 87.
    Rolls MM, Stein PA, Taylor SS, Ha E, McKeon F, Rapoport TA (1999) A visual screen of a GFP-fusion library identifies a new type of nuclear envelope membrane protein. J Cell Biol 146(1):29–44PubMedCentralPubMedCrossRefGoogle Scholar
  88. 88.
    Lin F, Blake DL, Callebaut I, Skerjanc IS, Holmer L, McBurney MW, Paulin-Levasseur M, Worman HJ (2000) MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. J Biol Chem 275(7):4840–4847PubMedCrossRefGoogle Scholar
  89. 89.
    Worman HJ, Yuan J, Blobel G, Georgatos SD (1988) A lamin B receptor in the nuclear envelope. Proc Natl Acad Sci U S A 85(22):8531–8534PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Senior A, Gerace L (1988) Integral membrane proteins specific to the inner nuclear membrane and associated with the nuclear lamina. J Cell Biol 107(6 Pt 1):2029–2036PubMedCrossRefGoogle Scholar
  91. 91.
    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(7): 1267–1279PubMedCrossRefGoogle Scholar
  92. 92.
    Hodzic DM, Yeater DB, Bengtsson L, Otto H, Stahl PD (2004) Sun2 is a novel mammalian inner nuclear membrane protein. J Biol Chem 279(24):25805–25812. doi: 10.1074/jbc.M313157200 PubMedCrossRefGoogle Scholar
  93. 93.
    Apel ED, Lewis RM, Grady RM, Sanes JR (2000) Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction. J Biol Chem 275(41):31986–31995. doi: 10.1074/jbc.M004775200 PubMedCrossRefGoogle Scholar
  94. 94.
    Clements L, Manilal S, Love DR, Morris GE (2000) Direct interaction between emerin and lamin A. Biochem Biophys Res Commun 267(3):709–714. doi: 10.1006/bbrc.1999.2023 PubMedCrossRefGoogle Scholar
  95. 95.
    Broers JL, Machiels BM, Kuijpers HJ, Smedts F, van den Kieboom R, Raymond Y, Ramaekers FC (1997) A- and B-type lamins are differentially expressed in normal human tissues. Histochem Cell Biol 107(6):505–517PubMedCrossRefGoogle Scholar
  96. 96.
    Inoue H, Kauffman M, Shacham S, Landesman Y, Yang J, Evans CP, Weiss RH (2013) CRM1 blockade by selective inhibitors of nuclear export attenuates kidney cancer growth. J Urol 189(6):2317–2326. doi: 10.1016/j.juro.2012.10.018 PubMedCrossRefGoogle Scholar
  97. 97.
    Tai YT, Landesman Y, Acharya C, Calle Y, Zhong MY, Cea M, Tannenbaum D, Cagnetta A, Reagan M, Munshi AA, Senapedis W, Saint-Martin JR, Kashyap T, Shacham S, Kauffman M, Gu Y, Wu L, Ghobrial I, Zhan F, Kung AL, Schey SA, Richardson P, Munshi NC, Anderson KC (2013) CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia. doi: 10.1038/leu.2013.115 PubMedCentralPubMedGoogle Scholar
  98. 98.
    Salas Fragomeni RA, Chung HW, Landesman Y, Senapedis W, Saint-Martin JR, Tsao H, Flaherty KT, Shacham S, Kauffman M, Cusack JC (2013) CRM1 and BRAF inhibition synergize and induce tumor regression in BRAF-mutant melanoma. Mol Cancer Ther 12(7):1171–1179. doi: 10.1158/1535-7163.MCT-12-1171 PubMedCrossRefGoogle Scholar
  99. 99.
    Walker CJ, Oaks JJ, Santhanam R, Neviani P, Harb JG, Ferenchak G, Ellis JJ, Landesman Y, Eisfeld AK, Gabrail NY, Smith CL, Caligiuri MA, Hokland P, Roy DC, Reid A, Milojkovic D, Goldman JM, Apperley J, Garzon R, Marcucci G, Shacham S, Kauffman MG, Perrotti D (2013) Preclinical and clinical efficacy of XPO1/CRM1 inhibition by the karyopherin inhibitor KPT-330 in Ph + leukemias. Blood 122(17):3034–3044. doi: 10.1182/blood-2013-04-495374 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Wellcome Trust Centre for Cell BiologyUniversity of EdinburghEdinburghUK
  2. 2.Wellcome Trust Centre for Cell BiologyUniversity of EdinburghEdinburghUK

Personalised recommendations