DOI QR코드

DOI QR Code

Functional roles of CTCF in breast cancer

  • Oh, Sumin (Laboratory of Biomedical Genomics, Department of Biological Science, Sookmyung Women's University) ;
  • Oh, Chaeun (Laboratory of Biomedical Genomics, Department of Biological Science, Sookmyung Women's University) ;
  • Yoo, Kyung Hyun (Laboratory of Biomedical Genomics, Department of Biological Science, Sookmyung Women's University)
  • Received : 2017.06.21
  • Published : 2017.09.30

Abstract

CTCF, Zinc-finger protein, has been identified as a multifunctional transcription factor that regulates gene expression through various mechanisms, including recruitment of other co-activators and binding to promoter regions of target genes. Furthermore, it has been proposed to be an insulator protein that contributes to the establishment of functional three-dimensional chromatin structures. It can disrupt transcription through blocking the connection between an enhancer and a promoter. Previous studies revealed that the onset of various diseases, including breast cancer, could be attributed to the aberrant expression of CTCF itself or one or more of its target genes. In this review, we will describe molecular dysfunction involving CTCF that induces tumorigenesis and summarize the functional roles of CTCF in breast cancer.

Keywords

References

  1. Filippova GN, Qi CF, Ulmer JE et al (2002) Tumorassociated zinc finger mutations in the CTCF transcription factor selectively alter tts DNA-binding specificity. Cancer Res 62, 48-52
  2. Nora EP, Goloborodko A, Valton AL et al (2017) Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization. Cell 169, 930-944 e922 https://doi.org/10.1016/j.cell.2017.05.004
  3. Fiorito E, Sharma Y, Gilfillan S et al (2016) CTCF modulates Estrogen Receptor function through specific chromatin and nuclear matrix interactions. Nucleic Acids Res 44, 10588-10602 https://doi.org/10.1093/nar/gkw785
  4. Barutcu AR, Lajoie BR, Fritz AJ et al (2016) SMARCA4 regulates gene expression and higher-order chromatin structure in proliferating mammary epithelial cells. Genome Res 26, 1188-1201 https://doi.org/10.1101/gr.201624.115
  5. Phillips JE and Corces VG (2009) CTCF: master weaver of the genome. Cell 137, 1194-1211 https://doi.org/10.1016/j.cell.2009.06.001
  6. Ong CT and Corces VG (2014) CTCF: an architectural protein bridging genome topology and function. Nat Rev Genet 15, 234-246 https://doi.org/10.1038/nrg3663
  7. Jerkovic I, Ibrahim DM, Andrey G et al (2017) Genome-Wide Binding of Posterior HOXA/D Transcription Factors Reveals Subgrouping and Association with CTCF. PLoS Genet 13, e1006567 https://doi.org/10.1371/journal.pgen.1006567
  8. Nakamoto M, Ishihara K, Watanabe T et al (2017) The Glucocorticoid Receptor Regulates the ANGPTL4 Gene in a CTCF-Mediated Chromatin Context in Human Hepatic Cells. PLoS One 12, e0169225 https://doi.org/10.1371/journal.pone.0169225
  9. Hsu SC, Gilgenast TG, Bartman CR et al (2017) The BET Protein BRD2 Cooperates with CTCF to Enforce Transcriptional and Architectural Boundaries. Mol Cell 66, 102-116 e107 https://doi.org/10.1016/j.molcel.2017.02.027
  10. Chen L, Zhao L, Alt FW and Krangel MS (2016) An Ectopic CTCF Binding Element Inhibits Tcrd Rearrangement by Limiting Contact between Vdelta and Ddelta Gene Segments. J Immunol 197, 3188-3197 https://doi.org/10.4049/jimmunol.1601124
  11. Braikia FZ, Oudinet C, Haddad D et al (2017) Inducible CTCF insulator delays the IgH 3' regulatory regionmediated activation of germline promoters and alters class switching. Proc Natl Acad Sci U S A 114, 6092-6097 https://doi.org/10.1073/pnas.1701631114
  12. Chan CS and Song JS (2008) CCCTC-binding factor confines the distal action of estrogen receptor. Cancer Res 68, 9041-9049 https://doi.org/10.1158/0008-5472.CAN-08-2632
  13. Nagy G, Czipa E, Steiner L et al (2016) Motif oriented high-resolution analysis of ChIP-seq data reveals the topological order of CTCF and cohesin proteins on DNA. BMC Genomics 17, 637 https://doi.org/10.1186/s12864-016-2940-7
  14. Gregor A, Oti M, Kouwenhoven EN et al (2013) De novo mutations in the genome organizer CTCF cause intellectual disability. Am J Hum Genet 93, 124-131 https://doi.org/10.1016/j.ajhg.2013.05.007
  15. Herold M, Bartkuhn M and Renkawitz R (2012) CTCF: insights into insulator function during development. Development 139, 1045-1057 https://doi.org/10.1242/dev.065268
  16. Bastaki F, Nair P, Mohamed M et al (2017) Identification of a novel CTCF mutation responsible for syndromic intellectual disability - a case report. BMC Med Genet 18, 68
  17. Prawitt D, Enklaar T, Gartner-Rupprecht B et al (2005) Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith- Wiedemann syndrome and Wilms' tumor. Proc Natl Acad Sci U S A 102, 4085-4090 https://doi.org/10.1073/pnas.0500037102
  18. Aulmann S, Blaker H, Penzel R, Rieker RJ, Otto HF and Sinn HP (2003) CTCF gene mutations in invasive ductal breast cancer. Breast Cancer Res Treat 80, 347-352 https://doi.org/10.1023/A:1024930404629
  19. Katainen R, Dave K, Pitkanen E et al (2015) CTCF/cohesin-binding sites are frequently mutated in cancer. Nat Genet 47, 818-821 https://doi.org/10.1038/ng.3335
  20. Chitayat D, Friedman JM, Anderson L and Dimmick JE (1988) Hepatocellular carcinoma in a child with familial Russell-Silver syndrome. Am J Med Genet 31, 909-914 https://doi.org/10.1002/ajmg.1320310425
  21. Bruckheimer E and Abrahamov A (1993) Russell-Silver syndrome and Wilms tumor. J Pediatr 122, 165-166
  22. Weiss GR and Garnick MB (1981) Testicular cancer in a Russell-Silver dwarf. J Urol 126, 836-837 https://doi.org/10.1016/S0022-5347(17)54773-4
  23. Draznin MB, Stelling MW and Johanson AJ (1980) Silver-Russell syndrome and craniopharyngioma. J Pediatr 96, 887-889 https://doi.org/10.1016/S0022-3476(80)80570-1
  24. Kemp CJ, Moore JM, Moser R et al (2014) CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Rep 7, 1020-1029 https://doi.org/10.1016/j.celrep.2014.04.004
  25. Suzuki H, Komiya A, Emi M et al (1996) Three distinct commonly deleted regions of chromosome arm 16q in human primary and metastatic prostate cancers. Genes Chromosomes Cancer 17, 225-233 https://doi.org/10.1002/(SICI)1098-2264(199612)17:4<225::AID-GCC4>3.0.CO;2-5
  26. Maw MA, Grundy PE, Millow LJ et al (1992) A third Wilms' tumor locus on chromosome 16q. Cancer Res 52, 3094-3098
  27. Cleton-Jansen AM, Moerland EW, Kuipers-Dijkshoorn NJ et al (1994) At least two different regions are involved in allelic imbalance on chromosome arm 16q in breast cancer. Genes Chromosomes Cancer 9, 101-107 https://doi.org/10.1002/gcc.2870090205
  28. Lindblom A, Rotstein S, Skoog L, Nordenskjold M and Larsson C (1993) Deletions on chromosome 16 in primary familial breast carcinomas are associated with development of distant metastases. Cancer Res 53, 3707-3711
  29. Kaiser VB, Taylor MS and Semple CA (2016) Mutational Biases Drive Elevated Rates of Substitution at Regulatory Sites across Cancer Types. PLoS Genet 12, e1006207 https://doi.org/10.1371/journal.pgen.1006207
  30. Poulos RC, Thoms JA, Guan YF, Unnikrishnan A, Pimanda JE and Wong JW (2016) Functional Mutations Form at CTCF-Cohesin Binding Sites in Melanoma Due to Uneven Nucleotide Excision Repair across the Motif. Cell Rep 17, 2865-2872 https://doi.org/10.1016/j.celrep.2016.11.055
  31. Zhou XL, Werelius B and Lindblom A (2004) A screen for germline mutations in the gene encoding CCCTC-binding factor (CTCF) in familial non-BRCA1/BRCA2 breast cancer. Breast Cancer Res 6, R187-190 https://doi.org/10.1186/bcr774
  32. Tiffen JC, Bailey CG, Marshall AD et al (2013) The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells. Int J Cancer 133, 1603-1613 https://doi.org/10.1002/ijc.28184
  33. Venkatraman B and Klenova E (2015) Role of CTCF poly(ADP-Ribosyl)ation in the regulation of apoptosis in breast cancer cells. Indian J Med Paediatr Oncol 36, 49-54 https://doi.org/10.4103/0971-5851.151784
  34. Torrano V, Navascues J, Docquier F et al (2006) Targeting of CTCF to the nucleolus inhibits nucleolar transcription through a poly(ADP-ribosyl)ation-dependent mechanism. J Cell Sci 119, 1746-1759 https://doi.org/10.1242/jcs.02890
  35. Docquier F, Kita GX, Farrar D et al (2009) Decreased poly(ADP-ribosyl)ation of CTCF, a transcription factor, is associated with breast cancer phenotype and cell proliferation. Clin Cancer Res 15, 5762-5771 https://doi.org/10.1158/1078-0432.CCR-09-0329
  36. Butcher DT and Rodenhiser DI (2007) Epigenetic inactivation of BRCA1 is associated with aberrant expression of CTCF and DNA methyltransferase (DNMT3B) in some sporadic breast tumours. Eur J Cancer 43, 210-219 https://doi.org/10.1016/j.ejca.2006.09.002
  37. Wang D, Li C and Zhang X (2014) The promoter methylation status and mRNA expression levels of CTCF and SIRT6 in sporadic breast cancer. DNA Cell Biol 33, 581-590 https://doi.org/10.1089/dna.2013.2257
  38. Del Campo EP, Marquez JJ, Reyes-Vargas F et al (2014) CTCF and CTCFL mRNA expression in 17beta-estradioltreated MCF7 cells. Biomed Rep 2, 101-104 https://doi.org/10.3892/br.2013.200
  39. Martin-Kleiner I (2012) BORIS in human cancers - a review. Eur J Cancer 48, 929-935 https://doi.org/10.1016/j.ejca.2011.09.009
  40. Mendez-Catala CF, Gretton S, Vostrov A et al (2013) A novel mechanism for CTCF in the epigenetic regulation of Bax in breast cancer cells. Neoplasia 15, 898-912 https://doi.org/10.1593/neo.121948
  41. Mustafa M, Lee JY and Kim MH (2015) CTCF negatively regulates HOXA10 expression in breast cancer cells. Biochem Biophys Res Commun 467, 828-834 https://doi.org/10.1016/j.bbrc.2015.10.058
  42. Teif VB, Beshnova DA, Vainshtein Y et al (2014) Nucleosome repositioning links DNA (de)methylation and differential CTCF binding during stem cell development. Genome Res 24, 1285-1295 https://doi.org/10.1101/gr.164418.113
  43. Wang H, Maurano MT, Qu H et al (2012) Widespread plasticity in CTCF occupancy linked to DNA methylation. Genome Res 22, 1680-1688 https://doi.org/10.1101/gr.136101.111
  44. Victoria-Acosta G, Vazquez-Santillan K, Jimenez-Hernandez L et al (2015) Epigenetic silencing of the XAF1 gene is mediated by the loss of CTCF binding. Sci Rep 5, 14838 https://doi.org/10.1038/srep14838
  45. Peng Z, Shen R, Li YW, Teng KY, Shapiro CL and Lin HJ (2012) Epigenetic repression of RARRES1 is mediated by methylation of a proximal promoter and a loss of CTCF binding. PLoS One 7, e36891 https://doi.org/10.1371/journal.pone.0036891
  46. Yao Z and Sherif ZA (2016) The effect of epigenetic silencing and TP53 mutation on the expression of DLL4 in human cancer stem disorder. Oncotarget 7, 62976-62988 https://doi.org/10.18632/oncotarget.11316
  47. de Souza Rocha Simonini P, Breiling A, Gupta N et al (2010) Epigenetically deregulated microRNA-375 is involved in a positive feedback loop with estrogen receptor alpha in breast cancer cells. Cancer Res 70, 9175-9184 https://doi.org/10.1158/0008-5472.CAN-10-1318
  48. Soto-Reyes E, Gonzalez-Barrios R, Cisneros-Soberanis F et al (2012) Disruption of CTCF at the miR-125b1 locus in gynecological cancers. BMC Cancer 12, 40 https://doi.org/10.1186/1471-2407-12-40
  49. Jiang F, Liu T, He Y et al (2011) MiR-125b promotes proliferation and migration of type II endometrial carcinoma cells through targeting TP53INP1 tumor suppressor in vitro and in vivo. BMC Cancer 11, 425 https://doi.org/10.1186/1471-2407-11-425
  50. Zhang Y, Liang J, Li Y et al (2010) CCCTC-binding factor acts upstream of FOXA1 and demarcates the genomic response to estrogen. J Biol Chem 285, 28604-28613 https://doi.org/10.1074/jbc.M110.149658
  51. Tang Z, Luo OJ, Li X et al (2015) CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Cell 163, 1611-1627 https://doi.org/10.1016/j.cell.2015.11.024
  52. Seitan VC, Faure AJ, Zhan Y et al (2013) Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments. Genome Res 23, 2066-2077 https://doi.org/10.1101/gr.161620.113
  53. Heidari N, Phanstiel DH, He C et al (2014) Genome-wide map of regulatory interactions in the human genome. Genome Res 24, 1905-1917 https://doi.org/10.1101/gr.176586.114
  54. Wu Q, Lian JB, Stein JL, Stein GS, Nickerson JA and Imbalzano AN (2017) The BRG1 ATPase of human SWI/SNF chromatin remodeling enzymes as a driver of cancer. Epigenomics 9, 919-931 https://doi.org/10.2217/epi-2017-0034
  55. Bai J, Mei P, Zhang C et al (2013) BRG1 is a prognostic marker and potential therapeutic target in human breast cancer. PLoS One 8, e59772 https://doi.org/10.1371/journal.pone.0059772
  56. Wu Q, Sharma S, Cui H et al (2016) Targeting the chromatin remodeling enzyme BRG1 increases the efficacy of chemotherapy drugs in breast cancer cells. Oncotarget 7, 27158-27175 https://doi.org/10.18632/oncotarget.8384
  57. Shukla S, Kavak E, Gregory M et al (2011) CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature 479, 74-79 https://doi.org/10.1038/nature10442
  58. Dutertre M, Gratadou L, Dardenne E et al (2010) Estrogen regulation and physiopathologic significance of alternative promoters in breast cancer. Cancer Res 70, 3760-3770 https://doi.org/10.1158/0008-5472.CAN-09-3988
  59. Ross-Innes CS, Brown GD and Carroll JS (2011) A co-ordinated interaction between CTCF and ER in breast cancer cells. BMC Genomics 12, 593 https://doi.org/10.1186/1471-2164-12-593
  60. Docquier F, Farrar D, D'Arcy V et al (2005) Heightened expression of CTCF in breast cancer cells is associated with resistance to apoptosis. Cancer Res 65, 5112-5122 https://doi.org/10.1158/0008-5472.CAN-03-3498
  61. Meeran SM, Patel SN and Tollefsbol TO (2010) Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PLoS One 5, e11457 https://doi.org/10.1371/journal.pone.0011457
  62. Klenova EM, Morse HC 3rd, Ohlsson R and Lobanenkov VV (2002) The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Semin Cancer Biol 12, 399-414 https://doi.org/10.1016/S1044-579X(02)00060-3
  63. D'Arcy V, Pore N, Docquier F et al (2008) BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours. Br J Cancer 98, 571-579 https://doi.org/10.1038/sj.bjc.6604181
  64. Dougherty CJ, Ichim TE, Liu L et al (2008) Selective apoptosis of breast cancer cells by siRNA targeting of BORIS. Biochem Biophys Res Commun 370, 109-112 https://doi.org/10.1016/j.bbrc.2008.03.040

Cited by

  1. Prognostic and Predictive Epigenetic Biomarkers in Oncology vol.23, pp.1, 2019, https://doi.org/10.1007/s40291-018-0371-7