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Open Access 07-10-2022 | Cancer Therapy | Non-Thematic Review

The role of inner nuclear membrane proteins in tumourigenesis and as potential targets for cancer therapy

Authors: Maddison Rose, Joshua T. Burgess, Kenneth O’Byrne, Derek J. Richard, Emma Bolderson

Published in: Cancer and Metastasis Reviews | Issue 4/2022

Abstract

Despite significant advances in our understanding of tumourigenesis and cancer therapeutics, cancer continues to account for 30% of worldwide deaths. Therefore, there remains an unmet need for the development of cancer therapies to improve patient quality of life and survival outcomes. The inner nuclear membrane has an essential role in cell division, cell signalling, transcription, cell cycle progression, chromosome tethering, cell migration and mitosis. Furthermore, expression of several inner nuclear membrane proteins has been shown to be frequently altered in tumour cells, resulting in the dysregulation of cellular pathways to promote tumourigenesis. However, to date, minimal research has been conducted to investigate how targeting these dysregulated and variably expressed proteins may provide a novel avenue for cancer therapies. In this review, we present an overview of the involvement of the inner nuclear membrane proteins within the hallmarks of cancer and how they may be exploited as potent anti-cancer therapeutics.

Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660CrossRef

Arruebo, M., Vilaboa, N., Sáez-Gutierrez, B., Lambea, J., Tres, A., Valladares, M., et al. (2011). Assessment of the evolution of cancer treatment therapies. Cancers (Basel), 3(3), 3279–3330. https://doi.org/10.3390/cancers3033279CrossRef

Davies, A., Lum, C., Raju, R., Ansell, E., Webber, K., & Segelov, E. (2021). Anti-cancer therapy made easier: A 25-year update. Internal Medicine Journal, 51(4), 473–480. https://doi.org/10.1111/imj.14878CrossRef

Sharma, P., Jhawat, V., Mathur, P., & Dutt, R. (2022). Innovation in cancer therapeutics and regulatory perspectives. Medical Oncology, 39(5), 76. https://doi.org/10.1007/s12032-022-01677-0CrossRef

Brown, R. (1833). Observations on the organs and mode of fecundation in Orchideae and Asclepiadeae. https://wellcomecollection.org/works/khgyheqh/items?canvas=4

Glavy, J. S., Krutchinsky, A. N., Cristea, I. M., Berke, I. C., Boehmer, T., Blobel, G., et al. (2007). Cell-cycle-dependent phosphorylation of the nuclear pore Nup107-160 subcomplex. Proc Natl Acad Sci USA, 104(10), 3811–3816. https://doi.org/10.1073/pnas.0700058104CrossRef

Rose, M., Bai, B., Tang, M., Cheong, C. M., Beard, S., Burgess, J. T., et al. (2021). The impact of rare human variants on barrier-to-auto-integration factor 1 (Banf1) structure and function. Front Cell Dev Biol, 9, 775441. https://doi.org/10.3389/fcell.2021.775441CrossRef

Gajewski, A., Csaszar, E., & Foisner, R. (2004). A phosphorylation cluster in the chromatin-binding region regulates chromosome association of LAP2alpha. Journal of Biological Chemistry, 279(34), 35813–35821. https://doi.org/10.1074/jbc.M402546200CrossRef

Gorjanacz, M. (2013). LEM-4 promotes rapid dephosphorylation of BAF during mitotic exit. Nucleus, 4(1), 14–17. https://doi.org/10.4161/nucl.22961CrossRef

10.

Laurell, E., Beck, K., Krupina, K., Theerthagiri, G., Bodenmiller, B., Horvath, P., et al. (2011). Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry. Cell, 144(4), 539–550. https://doi.org/10.1016/j.cell.2011.01.012CrossRef

11.

Peter, M., Nakagawa, J., Dorée, M., Labbé, J. C., & Nigg, E. A. (1990). In vitro disassembly of the nuclear lamina and M phase-specific phosphorylation of lamins by cdc2 kinase. Cell, 61(4), 591–602. https://doi.org/10.1016/0092-8674(90)90471-pCrossRef

12.

Zheng, Y., & Tsai, M. Y. (2006). The mitotic spindle matrix: A fibro-membranous lamin connection. Cell Cycle, 5(20), 2345–2347. https://doi.org/10.4161/cc.5.20.3365CrossRef

13.

Li, J., Wang, T., Pei, L., Jing, J., Hu, W., Sun, T., et al. (2017). Expression of VRK1 and the downstream gene BANF1 in esophageal cancer. Biomedicine & Pharmacotherapy, 89, 1086–1091. https://doi.org/10.1016/j.biopha.2017.02.095CrossRef

14.

von Appen, A., LaJoie, D., Johnson, I. E., Trnka, M. J., Pick, S. M., Burlingame, A. L., et al. (2020). LEM2 phase separation promotes ESCRT-mediated nuclear envelope reformation. Nature, 582(7810), 115–118. https://doi.org/10.1038/s41586-020-2232-xCrossRef

15.

Kim, D. I., Birendra, K. C., & Roux, K. J. (2015). Making the LINC: SUN and KASH protein interactions. Biological Chemistry, 396(4), 295–310. https://doi.org/10.1515/hsz-2014-0267CrossRef

16.

Zhuang, X., Semenova, E., Maric, D., & Craigie, R. (2014). Dephosphorylation of barrier-to-autointegration factor by protein phosphatase 4 and its role in cell mitosis. Journal of Biological Chemistry, 289(2), 1119–1127. https://doi.org/10.1074/jbc.M113.492777CrossRef

17.

Gao, A., Sun, T., Ma, G., Cao, J., Hu, Q., Chen, L., et al. (2018). LEM4 confers tamoxifen resistance to breast cancer cells by activating cyclin D-CDK4/6-Rb and ERalpha pathway. Nature Communications, 9(1), 4180. https://doi.org/10.1038/s41467-018-06309-8CrossRef

18.

Hetzer, M. W. (2010). The nuclear envelope. Cold Spring Harbor Perspectives in Biology, 2(3), a000539. https://doi.org/10.1101/cshperspect.a000539CrossRef

19.

Beck, M., & Hurt, E. (2017). The nuclear pore complex: Understanding its function through structural insight. Nature Reviews Molecular Cell Biology, 18(2), 73–89. https://doi.org/10.1038/nrm.2016.147CrossRef

20.

Blobel, G. (1985). Gene gating: A hypothesis. Proc Natl Acad Sci USA, 82(24), 8527–8529. https://doi.org/10.1073/pnas.82.24.8527CrossRef

21.

Kuhn, T. M., & Capelson, M. (2019). Nuclear pore proteins in regulation of chromatin state. Cells, 8(11), https://doi.org/10.3390/cells8111414

22.

Kalocsay, M., Hiller, N. J., & Jentsch, S. (2009). Chromosome-wide Rad51 spreading and SUMO-H2A.Z-dependent chromosome fixation in response to a persistent DNA double-strand break. Mol Cell, 33(3), 335–343. https://doi.org/10.1016/j.molcel.2009.01.016CrossRef

23.

Paquet, N., Box, J. K., Ashton, N. W., Suraweera, A., Croft, L. V., Urquhart, A. J., et al. (2014). Nestor-Guillermo Progeria Syndrome: A biochemical insight into Barrier-to-Autointegration Factor 1, alanine 12 threonine mutation. BMC Molecular Biology, 15, 27. https://doi.org/10.1186/s12867-014-0027-zCrossRef

24.

Alhudiri, I. M., Nolan, C. C., Ellis, I. O., Elzagheid, A., Rakha, E. A., Green, A. R., et al. (2019). Expression of Lamin A/C in early-stage breast cancer and its prognostic value. Breast Cancer Research and Treatment, 174(3), 661–668. https://doi.org/10.1007/s10549-018-05092-wCrossRef

25.

Abdelfatah, N., Chen, R., Duff, H. J., Seifer, C. M., Buffo, I., Huculak, C., et al. (2019). Characterization of a unique form of arrhythmic cardiomyopathy caused by recessive mutation in LEMD2. JACC Basic Transl Sci, 4(2), 204–221. https://doi.org/10.1016/j.jacbts.2018.12.001CrossRef

26.

Kreienkamp, R., & Gonzalo, S. (2019). Hutchinson-Gilford Progeria syndrome: Challenges at bench and bedside. SubCellular Biochemistry, 91, 435–451. https://doi.org/10.1007/978-981-13-3681-2_15CrossRef

27.

Atalaia, A., Ben Yaou, R., Wahbi, K., De Sandre-Giovannoli, A., Vigouroux, C., & Bonne, G. (2021). Laminopathies’ treatments systematic review: A contribution towards a “Treatabolome.” J Neuromuscul Dis, 8(3), 419–439. https://doi.org/10.3233/JND-200596CrossRef

28.

Belo, S. P., Magalhaes, A. C., Freitas, P., & Carvalho, D. M. (2015). Familial partial lipodystrophy, Dunnigan variety—challenges for patient care during pregnancy: A case report. BMC Research Notes, 8, 140. https://doi.org/10.1186/s13104-015-1065-4CrossRef

29.

Lee, Y., Lee, J. H., Park, H. J., & Choi, Y. C. (2017). Early-onset LMNA-associated muscular dystrophy with later involvement of contracture. Journal of Clinical Neurology, 13(4), 405–410. https://doi.org/10.3988/jcn.2017.13.4.405CrossRef

30.

Liang, J. J., Grogan, M., Ackerman, M. J., & Goodsell, K. (2016). LMNA-mediated arrhythmogenic right ventricular cardiomyopathy and charcot-Marie-tooth type 2B1: A patient-discovered unifying diagnosis. Journal of Cardiovascular Electrophysiology, 27(7), 868–871. https://doi.org/10.1111/jce.12984CrossRef

31.

Xu, Z., Yang, C., & Xue, R. (2021). Buschke-Ollendorff syndrome with LEMD3 germline stopgain mutation p.R678* presenting as multiple subcutaneous nodules with mucin deposition. J Cutan Pathol, 48(1), 77–80. https://doi.org/10.1111/cup.13771CrossRef

32.

Hutchinson, J. (1886). Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages, in a boy whose mother had been almost wholly bald from alopecia areata from the age of Six. Med Chir Trans, 69, 473–477. https://doi.org/10.1177/095952878606900127CrossRef

33.

Chen, L., Lee, L., Kudlow, B. A., Dos Santos, H. G., Sletvold, O., Shafeghati, Y., et al. (2003). LMNA mutations in atypical Werner’s syndrome. Lancet, 362(9382), 440–445. https://doi.org/10.1016/S0140-6736(03)14069-XCrossRef

34.

Terzano, G. H., & Mezzadra, J. M. (1947). Diagnosis of uterine cancer by vaginal smear. El Día Médico, 19(41), 1308–1313.

35.

Molitor, T. P., & Traktman, P. (2014). Depletion of the protein kinase VRK1 disrupts nuclear envelope morphology and leads to BAF retention on mitotic chromosomes. Molecular Biology of the Cell, 25(6), 891–903. https://doi.org/10.1091/mbc.E13-10-0603CrossRef

36.

Gorjanacz, M. (2014). Nuclear assembly as a target for anti-cancer therapies. Nucleus, 5(1), 47–55. https://doi.org/10.4161/nucl.27928CrossRef

37.

Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013CrossRef

38.

Martin, T. A., & Jiang, W. G. (2009). Loss of tight junction barrier function and its role in cancer metastasis. Biochimica et Biophysica Acta, 1788(4), 872–891. https://doi.org/10.1016/j.bbamem.2008.11.005CrossRef

39.

Chang, W., Folker, E. S., Worman, H. J., & Gundersen, G. G. (2013). Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts. Molecular Biology of the Cell, 24(24), 3869–3880. https://doi.org/10.1091/mbc.E13-06-0307CrossRef

40.

Folker, E. S., Ostlund, C., Luxton, G. W., Worman, H. J., & Gundersen, G. G. (2011). Lamin A variants that cause striated muscle disease are defective in anchoring transmembrane actin-associated nuclear lines for nuclear movement. Proc Natl Acad Sci USA, 108(1), 131–136. https://doi.org/10.1073/pnas.1000824108CrossRef

41.

Davidson, P. M., Denais, C., Bakshi, M. C., & Lammerding, J. (2014). Nuclear deformability constitutes a rate-limiting step during cell migration in 3-D environments. Cellular and Molecular Bioengineering, 7(3), 293–306. https://doi.org/10.1007/s12195-014-0342-yCrossRef

42.

Denais, C. M., Gilbert, R. M., Isermann, P., McGregor, A. L., te Lindert, M., Weigelin, B., et al. (2016). Nuclear envelope rupture and repair during cancer cell migration. Science, 352(6283), 353–358. https://doi.org/10.1126/science.aad7297CrossRef

43.

Vargas, J. D., Hatch, E. M., Anderson, D. J., & Hetzer, M. W. (2012). Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus, 3(1), 88–100. https://doi.org/10.4161/nucl.18954CrossRef

44.

Halfmann, C. T., Sears, R. M., Katiyar, A., Busselman, B. W., Aman, L. K., Zhang, Q., et al. (2019). Repair of nuclear ruptures requires barrier-to-autointegration factor. Journal of Cell Biology, 218(7), 2136–2149. https://doi.org/10.1083/jcb.201901116CrossRef

45.

Zheng, R., Ghirlando, R., Lee, M. S., Mizuuchi, K., Krause, M., & Craigie, R. (2000). Barrier-to-autointegration factor (BAF) bridges DNA in a discrete, higher-order nucleoprotein complex. Proc Natl Acad Sci USA, 97(16), 8997–9002. https://doi.org/10.1073/pnas.150240197CrossRef

46.

Ma, H., Qian, W., Bambouskova, M., Collins, P. L., Porter, S. I., Byrum, A. K., et al. (2020). Barrier-to-Autointegration Factor 1 Protects against a Basal cGAS-STING Response. mBio, 11(2), doi:https://doi.org/10.1128/mBio.00136-20.

47.

Guey, B., Wischnewski, M., Decout, A., Makasheva, K., Kaynak, M., Sakar, M. S., et al. (2020). BAF restricts cGAS on nuclear DNA to prevent innate immune activation. Science, 369(6505), 823–828. https://doi.org/10.1126/science.aaw6421CrossRef

48.

Swift, J., Ivanovska, I. L., Buxboim, A., Harada, T., Dingal, P. C., Pinter, J., et al. (2013). Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science, 341(6149), 1240104. https://doi.org/10.1126/science.1240104CrossRef

49.

Kong, L., Schafer, G., Bu, H., Zhang, Y., Zhang, Y., & Klocker, H. (2012). Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway. Carcinogenesis, 33(4), 751–759. https://doi.org/10.1093/carcin/bgs022CrossRef

50.

Willis, N. D., Cox, T. R., Rahman-Casans, S. F., Smits, K., Przyborski, S. A., van den Brandt, P., et al. (2008). Lamin A/C is a risk biomarker in colorectal cancer. PLoS ONE, 3(8), e2988. https://doi.org/10.1371/journal.pone.0002988CrossRef

51.

Otto, T., & Sicinski, P. (2017). Cell cycle proteins as promising targets in cancer therapy. Nature Reviews Cancer, 17(2), 93–115. https://doi.org/10.1038/nrc.2016.138CrossRef

52.

Lei, K., Zhu, X., Xu, R., Shao, C., Xu, T., Zhuang, Y., et al. (2012). Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response. Current Biology, 22(17), 1609–1615. https://doi.org/10.1016/j.cub.2012.06.043CrossRef

53.

Capo-chichi, C. D., Cai, K. Q., Smedberg, J., Ganjei-Azar, P., Godwin, A. K., & Xu, X. X. (2011). Loss of A-type lamin expression compromises nuclear envelope integrity in breast cancer. Chinese Journal of Cancer, 30(6), 415–425. https://doi.org/10.5732/cjc.010.10566CrossRef

54.

Asencio, C., Davidson, I. F., Santarella-Mellwig, R., Ly-Hartig, T. B., Mall, M., Wallenfang, M. R., et al. (2012). Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis. Cell, 150(1), 122–135. https://doi.org/10.1016/j.cell.2012.04.043CrossRef

55.

Capo-Chichi, C. D., Yeasky, T. M., Smith, E. R., & Xu, X. X. (2016). Nuclear envelope structural defect underlies the main cause of aneuploidy in ovarian carcinogenesis. BMC Cell Biology, 17(1), 37. https://doi.org/10.1186/s12860-016-0114-8CrossRef

56.

Dey, G., & Baum, B. (2021). Nuclear envelope remodelling during mitosis. Current Opinion in Cell Biology, 70, 67–74. https://doi.org/10.1016/j.ceb.2020.12.004CrossRef

57.

Schmidt, M., & Bastians, H. (2007). Mitotic drug targets and the development of novel anti-mitotic anticancer drugs. Drug Resist Updat, 10(4–5), 162–181. https://doi.org/10.1016/j.drup.2007.06.003CrossRef

58.

Dabauvalle, M. C., Muller, E., Ewald, A., Kress, W., Krohne, G., & Muller, C. R. (1999). Distribution of emerin during the cell cycle. European Journal of Cell Biology, 78(10), 749–756. https://doi.org/10.1016/S0171-9335(99)80043-0CrossRef

59.

Dubinska-Magiera, M., Koziol, K., Machowska, M., Piekarowicz, K., Filipczak, D., & Rzepecki, R. (2019). Emerin is required for proper nucleus reassembly after mitosis: Implications for new pathogenetic mechanisms for Laminopathies detected in EDMD1 patients. Cells, 8(3), https://doi.org/10.3390/cells8030240.

60.

Capo-chichi, C. D., Aguida, B., Chabi, N. W., Cai, Q. K., Offrin, G., Agossou, V. K., et al. (2016). Lamin A/C deficiency is an independent risk factor for cervical cancer. Cellular Oncology (Dordrecht), 39(1), 59–68. https://doi.org/10.1007/s13402-015-0252-6CrossRef

61.

Zhang, W., & Liu, H. T. (2002). MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Research, 12(1), 9–18. https://doi.org/10.1038/sj.cr.7290105CrossRef

62.

Dhillon, A. S., Hagan, S., Rath, O., & Kolch, W. (2007). MAP kinase signalling pathways in cancer. Oncogene, 26(22), 3279–3290. https://doi.org/10.1038/sj.onc.1210421CrossRef

63.

Lee, B., Lee, T. H., & Shim, J. (2017). Emerin suppresses Notch signaling by restricting the Notch intracellular domain to the nuclear membrane. Biochimica et Biophysica Acta, Molecular Cell Research, 1864(2), 303–313. https://doi.org/10.1016/j.bbamcr.2016.11.013CrossRef

64.

Muchir, A., Wu, W., & Worman, H. J. (2009). Reduced expression of A-type lamins and emerin activates extracellular signal-regulated kinase in cultured cells. Biochimica et Biophysica Acta, 1792(1), 75–81. https://doi.org/10.1016/j.bbadis.2008.10.012CrossRef

65.

Lin, F., Morrison, J. M., Wu, W., & Worman, H. J. (2005). MAN1, an integral protein of the inner nuclear membrane, binds Smad2 and Smad3 and antagonizes transforming growth factor-beta signaling. Human Molecular Genetics, 14(3), 437–445. https://doi.org/10.1093/hmg/ddi040CrossRef

66.

Koveitypour, Z., Panahi, F., Vakilian, M., Peymani, M., Seyed Forootan, F., Nasr Esfahani, M. H., et al. (2019). Signaling pathways involved in colorectal cancer progression. Cell & Bioscience, 9, 97. https://doi.org/10.1186/s13578-019-0361-4CrossRef

67.

Pan, D., Estevez-Salmeron, L. D., Stroschein, S. L., Zhu, X., He, J., Zhou, S., et al. (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. Journal of Biological Chemistry, 280(16), 15992–16001. https://doi.org/10.1074/jbc.M411234200CrossRef

68.

Kong, Y., Zhang, Y., Wang, H., Kan, W., Guo, H., Liu, Y., et al. (2022). Inner nuclear membrane protein TMEM201 promotes breast cancer metastasis by positive regulating TGFbeta signaling. Oncogene, 41(5), 647–656. https://doi.org/10.1038/s41388-021-02098-5CrossRef

69.

Wu, G., Weng, W., Xia, P., Yan, S., Zhong, C., Xie, L., et al. (2021). Wnt signalling pathway in bladder cancer. Cellular Signalling, 79, 109886. https://doi.org/10.1016/j.cellsig.2020.109886CrossRef

70.

Shaw, H. V., Koval, A., & Katanaev, V. L. (2019). Targeting the Wnt signalling pathway in cancer: Prospects and perils. Swiss Medical Weekly, 149, w20129. https://doi.org/10.4414/smw.2019.20129CrossRef

71.

Markiewicz, E., Tilgner, K., Barker, N., van de Wetering, M., Clevers, H., Dorobek, M., et al. (2006). The inner nuclear membrane protein emerin regulates beta-catenin activity by restricting its accumulation in the nucleus. EMBO Journal, 25(14), 3275–3285. https://doi.org/10.1038/sj.emboj.7601230CrossRef

72.

Liddane, A. G., McNamara, C. A., Campbell, M. C., Mercier, I., & Holaska, J. M. (2021). Defects in Emerin-Nucleoskeleton binding disrupt nuclear structure and promote breast cancer cell motility and metastasis. Molecular Cancer Research, 19(7), 1196–1207. https://doi.org/10.1158/1541-7786.MCR-20-0413CrossRef

73.

Kim, H. J., Hwang, S. H., Han, M. E., Baek, S., Sim, H. E., Yoon, S., et al. (2012). LAP2 is widely overexpressed in diverse digestive tract cancers and regulates motility of cancer cells. PLoS ONE, 7(6), e39482. https://doi.org/10.1371/journal.pone.0039482CrossRef

74.

Parise, P., Finocchiaro, G., Masciadri, B., Quarto, M., Francois, S., Mancuso, F., et al. (2006). Lap2alpha expression is controlled by E2F and deregulated in various human tumors. Cell Cycle, 5(12), 1331–1341. https://doi.org/10.4161/cc.5.12.2833CrossRef

75.

Ozaki, T., & Nakagawara, A. (2011). Role of p53 in cell death and human cancers. Cancers (Basel), 3(1), 994–1013. https://doi.org/10.3390/cancers3010994CrossRef

76.

Somech, R., Shaklai, S., Geller, O., Amariglio, N., Simon, A. J., Rechavi, G., et al. (2005). The nuclear-envelope protein and transcriptional repressor LAP2beta interacts with HDAC3 at the nuclear periphery, and induces histone H4 deacetylation. Journal of Cell Science, 118(Pt 17), 4017–4025. https://doi.org/10.1242/jcs.02521CrossRef

77.

Bolderson, E., Burgess, J. T., Li, J., Gandhi, N. S., Boucher, D., Croft, L. V., et al. (2019). Barrier-to-autointegration factor 1 (Banf1) regulates poly [ADP-ribose] polymerase 1 (PARP1) activity following oxidative DNA damage. Nature Communications, 10(1), 5501. https://doi.org/10.1038/s41467-019-13167-5CrossRef

78.

Burgess, J. T., Cheong, C. M., Suraweera, A., Sobanski, T., Beard, S., Dave, K., et al. (2021). Barrier-to-autointegration-factor (Banf1) modulates DNA double-strand break repair pathway choice via regulation of DNA-dependent kinase (DNA-PK) activity. Nucleic Acids Research, 49(6), 3294–3307. https://doi.org/10.1093/nar/gkab110CrossRef

79.

Moser, B., Basilio, J., Gotzmann, J., Brachner, A., & Foisner, R. (2020). Comparative interactome analysis of Emerin, MAN1 and LEM2 reveals a unique role for LEM2 in nucleotide excision repair. Cells, 9(2). https://doi.org/10.3390/cells9020463.

80.

Scully, R., Panday, A., Elango, R., & Willis, N. A. (2019). DNA double-strand break repair-pathway choice in somatic mammalian cells. Nature Reviews Molecular Cell Biology, 20(11), 698–714. https://doi.org/10.1038/s41580-019-0152-0CrossRef

81.

Heidenreich, E., Novotny, R., Kneidinger, B., Holzmann, V., & Wintersberger, U. (2003). Non-homologous end joining as an important mutagenic process in cell cycle-arrested cells. EMBO Journal, 22(9), 2274–2283. https://doi.org/10.1093/emboj/cdg203CrossRef

82.

Maynard, S., Keijzers, G., Akbari, M., Ezra, M. B., Hall, A., Morevati, M., et al. (2019). Lamin A/C promotes DNA base excision repair. Nucleic Acids Research, 47(22), 11709–11728. https://doi.org/10.1093/nar/gkz912CrossRef

83.

Gibbs-Seymour, I., Markiewicz, E., Bekker-Jensen, S., Mailand, N., & Hutchison, C. J. (2015). Lamin A/C-dependent interaction with 53BP1 promotes cellular responses to DNA damage. Aging Cell, 14(2), 162–169. https://doi.org/10.1111/acel.12258CrossRef

84.

Lamm, N., Rogers, S., & Cesare, A. J. (2021). Chromatin mobility and relocation in DNA repair. Trends in Cell Biology, 31(10), 843–855. https://doi.org/10.1016/j.tcb.2021.06.002CrossRef

85.

Nagai, S., Dubrana, K., Tsai-Pflugfelder, M., Davidson, M. B., Roberts, T. M., Brown, G. W., et al. (2008). Functional targeting of DNA damage to a nuclear pore-associated SUMO-dependent ubiquitin ligase. Science, 322(5901), 597–602. https://doi.org/10.1126/science.1162790CrossRef

86.

Ryu, T., Spatola, B., Delabaere, L., Bowlin, K., Hopp, H., Kunitake, R., et al. (2015). Heterochromatic breaks move to the nuclear periphery to continue recombinational repair. Nature Cell Biology, 17(11), 1401–1411. https://doi.org/10.1038/ncb3258CrossRef

87.

Rose, M., Burgess, J. T., O’Byrne, K., Richard, D. J., & Bolderson, E. (2020). PARP inhibitors: Clinical relevance, mechanisms of action and tumor resistance. Front Cell Dev Biol, 8, 564601. https://doi.org/10.3389/fcell.2020.564601CrossRef

88.

Dechat, T., Shimi, T., Adam, S. A., Rusinol, A. E., Andres, D. A., Spielmann, H. P., et al. (2007). Alterations in mitosis and cell cycle progression caused by a mutant lamin A known to accelerate human aging. Proc Natl Acad Sci USA, 104(12), 4955–4960. https://doi.org/10.1073/pnas.0700854104CrossRef

89.

Cao, K., Capell, B. C., Erdos, M. R., Djabali, K., & Collins, F. S. (2007). A lamin A protein isoform overexpressed in Hutchinson-Gilford progeria syndrome interferes with mitosis in progeria and normal cells. Proc Natl Acad Sci USA, 104(12), 4949–4954. https://doi.org/10.1073/pnas.0611640104CrossRef

90.

Gonzalo, S., & Kreienkamp, R. (2015). DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome. Current Opinion in Cell Biology, 34, 75–83. https://doi.org/10.1016/j.ceb.2015.05.007CrossRef

91.

Wei, X. X., Siegel, A. P., Aggarwal, R., Lin, A. M., Friedlander, T. W., Fong, L., et al. (2018). A phase II trial of Selinexor, an oral selective inhibitor of nuclear export compound, in Abiraterone- and/or Enzalutamide-refractory metastatic castration-resistant prostate cancer. The Oncologist, 23(6), 656-e664. https://doi.org/10.1634/theoncologist.2017-0624CrossRef

92.

Shao, C., Lu, C., Chen, L., Koty, P. P., Cobos, E., & Gao, W. (2011). p53-Dependent anticancer effects of leptomycin B on lung adenocarcinoma. Cancer Chemotherapy and Pharmacology, 67(6), 1369–1380. https://doi.org/10.1007/s00280-010-1434-6CrossRef

93.

Sakakibara, K., Saito, N., Sato, T., Suzuki, A., Hasegawa, Y., Friedman, J. M., et al. (2011). CBS9106 is a novel reversible oral CRM1 inhibitor with CRM1 degrading activity. Blood, 118(14), 3922–3931. https://doi.org/10.1182/blood-2011-01-333138CrossRef

94.

Turner, J. G., Cui, Y., Bauer, A. A., Dawson, J. L., Gomez, J. A., Kim, J., et al. (2020). Melphalan and Exportin 1 inhibitors exert synergistic antitumor effects in preclinical models of human multiple myeloma. Cancer Research, 80(23), 5344–5354. https://doi.org/10.1158/0008-5472.CAN-19-0677CrossRef

95.

Sadowski, A. R., Gardner, H. L., Borgatti, A., Wilson, H., Vail, D. M., Lachowicz, J., et al. (2018). Phase II study of the oral selective inhibitor of nuclear export (SINE) KPT-335 (verdinexor) in dogs with lymphoma. BMC Veterinary Research, 14(1), 250. https://doi.org/10.1186/s12917-018-1587-9CrossRef

96.

Stefanello, S. T., Luchtefeld, I., Liashkovich, I., Petho, Z., Azzam, I., Bulk, E., et al. (2021). Impact of the nuclear envelope on malignant transformation, motility, and survival of lung cancer cells. Adv Sci (Weinh), 8(22), e2102757. https://doi.org/10.1002/advs.202102757CrossRef

Title: The role of inner nuclear membrane proteins in tumourigenesis and as potential targets for cancer therapy
Authors: Maddison Rose
Joshua T. Burgess
Kenneth O’Byrne
Derek J. Richard
Emma Bolderson
Publication date: 07-10-2022
Publisher: Springer US
Keyword: Cancer Therapy
Published in: Cancer and Metastasis Reviews / Issue 4/2022
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-022-10065-z

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