The Triple-Code Model for Pancreatic Cancer: Cross Talk Among Genetics, Epigenetics, and Nuclear Structure

Surgical Clinics of North America

Volumn 95, Issue 5, 2015, Pages 935-952

  Lomberk, Gwen A ^a   Urrutia, Raul ^a,b  

^a MAYO CLINIC   (United States)

^b MAYO GRADUATE SCHOOL   (United States)

Author keywords

Epigenetics; Pancreatic adenocarcinoma; Triple code hypothesis

Indexed keywords

GENOMIC DNA; MESSENGER RNA; TRANSCRIPTION FACTOR; TUMOR MARKER; UNTRANSLATED RNA; NUCLEOSOME;

CANCER GENETICS; CARCINOGENESIS; CHROMATIN; DNA METHYLATION; DNA MODIFICATION; EPIGENETICS; GENE EXPRESSION; GENETIC REGULATION; HUMAN; MOLECULAR INTERACTION; NONHUMAN; NUCLEOSOME; PANCREAS CANCER; PHENOTYPE; PRIORITY JOURNAL; REVIEW; ADENOCARCINOMA; BIOLOGICAL MODEL; GENETIC EPIGENESIS; GENETICS; MUTATION; PANCREAS TUMOR;

ADENOCARCINOMA; BIOMARKERS, TUMOR; EPIGENESIS, GENETIC; HUMANS; MODELS, GENETIC; MUTATION; NUCLEOSOMES; PANCREATIC NEOPLASMS;

EID: 84940614230     PISSN: 00396109     EISSN: 15583171     Source Type: Journal    
DOI: 10.1016/j.suc.2015.05.011     Document Type: Review

References (115)

1. Iovanna J., Mallmann M., Goncalves A., et al. Current knowledge on pancreatic cancer. Front Oncol 2012, 2:6.
2. Sharma C., Eltawil K., Renfrew P., et al. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol 2011, 17:867-897.
3. Yu X., Zhang Y., Chen C., et al. Targeted drug delivery in pancreatic cancer. Biochim Biophys Acta 2010, 1805:97-104.
4. Burris H., Moore M., Andersen J., et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 1997, 15:2403-2413.
5. Heinemann V. Gemcitabine: progress in the treatment of pancreatic cancer. Oncology 2001, 60:8-18.
6. Rocha Lima C., Green M., Rotche R., et al. Irinotecan plus gemcitabine results in no survival advantage compared with gemcitabine monotherapy in patients with locally advanced or metastatic pancreatic cancer despite increased tumor response rate. J Clin Oncol 2004, 22:3776-3783.
7. Louvet C., Labianca R., Hammel P., et al. Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 2005, 23:3509-3516.
8. Scheithauer W., Schull B., Ulrich-Pur H., et al. Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial. Ann Oncol 2003, 14:97-104.
9. Hruban R.H., Goggins M., Parsons J., et al. Progression model for pancreatic cancer. Clin Cancer Res 2000, 6:2969-2972.
10. Kanda M., Matthaei H., Wu J., et al. Presence of somatic mutations in most early-stage pancreatic intraepithelial neoplasia. Gastroenterology 2012, 142:730-733.e739.
11. Rivera J.A., Rall C.J.N., Graeme-Cook F., et al. Analysis of K-ras oncogene mutations in chronic pancreatitis with ductal hyperplasia. Surgery 1997, 121:42-49.
12. Herreros-Villanueva M., Hijona E., Cosme A., et al. Mouse models of pancreatic cancer. World J Gastroenterol 2012, 18:1286-1294.
13. Perez-Mancera P.A., Guerra C., Barbacid M., et al. What we have learned about pancreatic cancer from mouse models. Gastroenterology 2012, 142:1079-1092.
14. Waddington C.H. The epigenotype. 1942. Int J Epidemiol 2012, 41:10-13.
15. Colman A. Profile of John Gurdon and Shinya Yamanaka, 2012 nobel laureates in medicine or physiology. Proc Natl Acad Sci U S A 2013, 110:5740-5741.
16. Egger G., Liang G., Aparicio A., et al. Epigenetics in human disease and prospects for epigenetic therapy. Nature 2004, 429:457-463.
17. Ho S.-M., Johnson A., Tarapore P., et al. Environmental epigenetics and its implication on disease risk and health outcomes. ILAR J 2012, 53:289-305.
18. Lomberk G., Urrutia R. Epigenetics and its applications to a revised progression model of pancreatic cancer. Pancreatic cancer 2010, 143-169. Springer, New York. J.P. Neoptolemos, R. Urrutia, J.L. Abbruzzese (Eds.).
19. Maitra A., Fukushima N., Takaori K., et al. Precursors to invasive pancreatic cancer. Adv Anat Pathol 2005, 12:81-91.
20. Frese K.K., Tuveson D.A. Maximizing mouse cancer models. Nat Rev Cancer 2007, 7:654-658.
21. Mazzio E.A., Soliman K.F.A. Basic concepts of epigenetics: impact of environmental signals on gene expression. Epigenetics 2012, 7:119-130.
22. Strahl B.D., Allis C.D. The language of covalent histone modifications. Nature 2000, 403:41-45.
23. Turner B.M. Histone acetylation and an epigenetic code. Bioessays 2000, 22:836-845.
24. Seligson D.B., Horvath S., McBrian M.A., et al. Global levels of histone modifications predict prognosis in different cancers. Am J Pathol 2009, 174:1619-1628.
25. Esteller M. The necessity of a human epigenome project. Carcinogenesis 2006, 27:1121-1125.
26. Kanai Y., Arai E. Multilayer-omics analyses of human cancers: exploration of biomarkers and drug targets based on the activities of the International Human Epigenome Consortium. Front Genet 2014, 5:24.
27. Manuyakorn A., Paulus R., Farrell J., et al. Cellular histone modification patterns predict prognosis and treatment response in resectable pancreatic adenocarcinoma: results from RTOG 9704. J Clin Oncol 2010, 28:1358-1365.
28. Lomberk G., Urrutia R. The family feud: turning off Sp1 by Sp1-like KLF proteins. Biochem J 2005, 392:1-11.
29. Freeman J.A., Espinosa J.M. The impact of post-transcriptional regulation in the p53 network. Brief Funct Genomics 2013, 12:46-57.
30. Koorstra J.-B.M., Hustinx S.R., Offerhaus G.J.A., et al. Pancreatic carcinogenesis. Pancreatology 2008, 8:110-125.
31. Rivlin N., Brosh R., Oren M., et al. Mutations in the p53 tumor suppressor gene: important milestones at the various steps of tumorigenesis. Genes Cancer 2011, 2:466-474.
32. Lusser A., Kadonaga J.T. Chromatin remodeling by ATP-dependent molecular machines. Bioessays 2003, 25:1192-1200.
33. Shain A.H., Pollack J.R. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLoS One 2013, 8:e55119.
34. Mazur P.K., Reynoird N., Khatri P., et al. SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 2014, 510:283-287.
35. Ougolkov A.V., Bilim V.N., Billadeau D.D. Regulation of pancreatic tumor cell proliferation and chemoresistance by the histone methyltransferase enhancer of zeste homologue 2. Clin Cancer Res 2008, 14:6790-6796.
36. Qazi A.M., Aggarwal S., Steffer C.S., et al. Laser capture microdissection of pancreatic ductal adeno-carcinoma cells to analyze EzH2 by Western Blot analysis. Methods Mol Biol 2011, 755:245-256.
37. Toll A.D., Dasgupta A., Potoczek M., et al. Implications of enhancer of zeste homologue 2 expression in pancreatic ductal adenocarcinoma. Hum Pathol 2010, 41:1205-1209.
38. Fujii S., Fukamachi K., Tsuda H., et al. RAS oncogenic signal upregulates EZH2 in pancreatic cancer. Biochem Biophys Res Commun 2012, 417:1074-1079.
39. Lasfargues C., Pyronnet S. EZH2 links pancreatitis to tissue regeneration and pancreatic cancer. Clin Res Hepatol Gastroenterol 2012, 36:323-324.
40. van Vlerken L.E., Kiefer C.M., Morehouse C., et al. EZH2 Is required for breast and pancreatic cancer stem cell maintenance and can be used as a functional cancer stem cell reporter. Stem Cells Translational Med 2013, 2:43-52.
41. Tzatsos A., Paskaleva P., Ferrari F., et al. KDM2B promotes pancreatic cancer via Polycomb-dependent and -independent transcriptional programs. J Clin Invest 2013, 123:727-739.
42. Qin Y., Zhu W., Xu W., et al. LSD1 sustains pancreatic cancer growth via maintaining HIF1α-dependent glycolytic process. Cancer Lett 2014, 347:225-232.
43. Yamamoto K., Tateishi K., Kudo Y., et al. Loss of histone demethylase KDM6B enhances aggressiveness of pancreatic cancer through downregulation of C/EBPα. Carcinogenesis 2014, 35:2404-2414.
44. Lehmann A., Denkert C., Budczies J., et al. High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo. BMC Cancer 2009, 9:395.
45. Nakagawa M., Oda Y., Eguchi T., et al. Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep 2007, 18:769-774.
46. Miyake K., Yoshizumi T., Imura S., et al. Expression of hypoxia-inducible factor-1alpha, histone deacetylase 1, and metastasis-associated protein 1 in pancreatic carcinoma: correlation with poor prognosis with possible regulation. Pancreas 2008, 36:e1-e9.
47. Wang W., Gao J., Man X.H., et al. Significance of DNA methyltransferase-1 and histone deacetylase-1 in pancreatic cancer. Oncol Rep 2009, 21:1439-1447.
48. Fritsche P., Seidler B., Schüler S., et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA. Gut 2009, 58:1399-1409.
49. Ouaïssi M., Sielezneff I., Silvestre R., et al. High histone deacetylase 7 (HDAC7) expression is significantly associated with adenocarcinomas of the pancreas. Ann Surg Oncol 2008, 15:2318-2328.
50. Yun M., Wu J., Workman J.L., et al. Readers of histone modifications. Cell Res 2011, 21:564-578.
51. Kouzarides T. Chromatin modifications and their function. Cell 2007, 128:693-705.
52. Izzo A., Schneider R. Chatting histone modifications in mammals. Brief Funct Genomics 2010, 9:429-443.
53. Kim Y.Z. Altered histone modifications in gliomas. Brain Tumor Res Treat 2014, 2:7-21.
54. Ivanov M., Barragan I., Ingelman-Sundberg M. Epigenetic mechanisms of importance for drug treatment. Trends Pharmacol Sci 2014, 35:384-396.
55. Rotili D., Mai A. Targeting histone demethylases: a new avenue for the fight against cancer. Genes Cancer 2011, 2:663-679.
56. Arrowsmith C.H., Bountra C., Fish P.V., et al. Epigenetic protein families: a new frontier for drug discovery. Nat Rev Drug Discov 2012, 11:384-400.
57. Bird A.P., Wolffe A.P. Methylation-induced repression-belts, braces, and chromatin. Cell 1999, 99:451-454.
58. Jones P.A. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012, 13:484-492.
59. Kohli R.M., Zhang Y. TET enzymes, TDG and the dynamics of DNA demethylation. Nature 2013, 502:472-479.
60. Perini G., Diolaiti D., Porro A., et al. In vivo transcriptional regulation of N-Myc target genes is controlled by E-box methylation. Proc Natl Acad Sci U S A 2005, 102:12117-12122.
61. Subramaniam D., Thombre R., Dhar A., et al. DNA methyltransferases: a novel target for prevention and therapy. Front Oncol 2014, 4:80.
62. Parry L., Clarke A.R. The roles of the Methyl-CpG binding proteins in cancer. Genes Cancer 2011, 2:618-630.
63. Liyanage V.R.B., Jarmasz J.S., Murugeshan N., et al. DNA modifications: function and applications in normal and disease states. Biology (Basel) 2014, 3:670-723.
64. Kaelin W.G., McKnight S.L. Influence of metabolism on epigenetics and disease. Cell 2013, 153:56-69.
65. Ueki T., Toyota M., Sohn T., et al. Hypermethylation of multiple genes in pancreatic adenocarcinoma. Cancer Res 2000, 60:1835-1839.
66. Shakya R., Gonda T., Quante M., et al. Hypomethylating therapy in an aggressive stroma-rich model of pancreatic carcinoma. Cancer Res 2013, 73:885-896.
67. Missiaglia E., Donadelli M., Palmieri M., et al. Growth delay of human pancreatic cancer cells by methylase inhibitor 5-aza-2'-deoxycytidine treatment is associated with activation of the interferon signalling pathway. Oncogene 2005, 24:199-211.
68. Ehrlich M. DNA hypomethylation in cancer cells. Epigenomics 2009, 1:239-259.
69. Yang H., Liu Y., Bai F., et al. Tumor development is associated with decrease of TET gene expression and 5-methylcytosine hydroxylation. Oncogene 2013, 32:663-669.
70. Matsubayashi H., Canto M., Sato N., et al. DNA methylation alterations in the pancreatic juice of patients with suspected pancreatic disease. Cancer Res 2006, 66:1208-1217.
71. Fukushima N., Walter K.M., Uek T., et al. Diagnosing pancreatic cancer using methylation specific PCR analysis of pancreatic juice. Cancer Biol Ther 2003, 2:78-83.
72. Dauksa A., Gulbinas A., Barauskas G., et al. Whole blood DNA aberrant methylation in pancreatic adenocarcinoma shows association with the course of the disease: a pilot study. PLoS One 2012, 7:e37509.
73. Kisiel J.B., Yab T.C., Taylor W.R., et al. Stool DNA testing for the detection of pancreatic cancer: assessment of methylation marker candidates. Cancer 2012, 118:2623-2631.
74. Santosh B., Varshney A., Yadava P.K. Non-coding RNAs: biological functions and applications. Cell Biochem Funct 2015, 33:14-22.
75. Taft R.J., Pang K.C., Mercer T.R., et al. Non-coding RNAs: regulators of disease. J Pathol 2010, 220:126-139.
76. Ghildiyal M., Zamore P.D. Small silencing RNAs: an expanding universe. Nat Rev Genet 2009, 10:94-108.
77. Seto A.G., Kingston R.E., Lau N.C. The coming of age for Piwi proteins. Mol Cell 2007, 26:603-609.
78. Malone C.D., Hannon G.J. Small RNAs as guardians of the genome. Cell 2009, 136:656-668.
79. Li X., Wu Z., Fu X., et al. lncRNAs: insights into their function and mechanics in underlying disorders. Mutat Res Rev Mutat Res 2014, 762:1-21.
80. Kaikkonen M.U., Lam M.T.Y., Glass C.K. Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res 2011, 90:430-440.
81. Ma M.-Z., Kong X., Weng M.-Z., et al. Candidate microRNA biomarkers of pancreatic ductal adenocarcinoma: meta-analysis, experimental validation and clinical significance. J Exp Clin Cancer Res 2013, 32:71.
82. Sun T., Kong X., Du Y., et al. Aberrant MicroRNAs in Pancreatic Cancer: Researches and Clinical Implications. Gastroenterol Res Pract 2014, 2014:386561.
83. Kim K., Jutooru I., Chadalapaka G., et al. HOTAIR is a negative prognostic factor and exhibits pro-oncogenic activity in pancreatic cancer. Oncogene 2013, 32:1616-1625.
84. Huang C.S., Yu W., Cui H., et al. Increased expression of the lncRNA PVT1 is associated with poor prognosis in pancreatic cancer patients. Minerva Med 2015, 106(3):143-149.
85. Pang E.J., Yang R., Fu X.B., et al. Overexpression of long non-coding RNA MALAT1 is correlated with clinical progression and unfavorable prognosis in pancreatic cancer. Tumour Biol 2015, 36(4):2403-2407.
86. Peng W., Gao W., Feng J. Long noncoding RNA HULC is a novel biomarker of poor prognosis in patients with pancreatic cancer. Med Oncol 2014, 31:346.
87. Li J., Liu D., Hua R., et al. Long non-coding RNAs expressed in pancreatic ductal adenocarcinoma and lncRNA BC008363 an independent prognostic factor in PDAC. Pancreatology 2014, 14:385-390.
88. Sun Y.W., Chen Y.F., Li J., et al. A novel long non-coding RNA ENST00000480739 suppresses tumour cell invasion by regulating OS-9 and HIF-1[alpha] in pancreatic ductal adenocarcinoma. Br J Cancer 2014, 111:2131-2141.
89. Hruban R.H., Adsay N.V., Albores-Saavedra J., et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am J Surg Pathol 2001, 25:579-586.
90. Reddy K.L., Feinberg A.P. Higher order chromatin organization in cancer. Semin Cancer Biol 2013, 23:109-115.
91. Chow K.-H., Factor R.E., Ullman K.S. The nuclear envelope environment and its cancer connections. Nat Rev Cancer 2012, 12:196-209.
92. Linder S., Lindholm J., Falkmer U., et al. Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas. Int J Pancreatol 1995, 18:241-248.
93. Vasilescu C., Giza D.E., Petrisor P., et al. Morphometrical differences between resectable and non-resectable pancreatic cancer: a fractal analysis. Hepatogastroenterology 2012, 59:284-288.
94. Timme S., Schmitt E., Stein S., et al. Nuclear position and shape deformation of chromosome 8 territories in pancreatic ductal adenocarcinoma. Anal Cell Pathol (Amst) 2011, 34:21-33.
95. Fernandez-Zapico M.E., Lomberk G.A., Tsuji S., et al. A functional family-wide screening of SP/KLF proteins identifies a subset of suppressors of KRAS-mediated cell growth. Biochem J 2011, 435:529-537.
96. Fernandez-Zapico M.E., Mladek A., Ellenrieder V., et al. An mSin3A interaction domain links the transcriptional activity of KLF11 with its role in growth regulation. EMBO J 2003, 22:4748-4758.
97. Truty M.J., Lomberk G., Fernandez-Zapico M.E., et al. Silencing of the transforming growth factor-beta (TGFbeta) receptor II by Kruppel-like factor 14 underscores the importance of a negative feedback mechanism in TGFbeta signaling. J Biol Chem 2009, 284:6291-6300.
98. Calvo E., Grzenda A., Lomberk G., et al. Single and combinatorial chromatin coupling events underlies the function of transcript factor Krüppel-like factor 11 in the regulation of gene networks. BMC Mol Biol 2014, 15:10.
99. Loft A., Forss I., Siersbaek M.S., et al. Browning of human adipocytes requires KLF11 and reprogramming of PPARgamma superenhancers. Genes Dev 2015, 29:7-22.
100. Lomberk G., Grzenda A., Mathison A., et al. Kruppel-like factor 11 regulates the expression of metabolic genes via an evolutionarily conserved protein interaction domain functionally disrupted in maturity onset diabetes of the young. J Biol Chem 2013, 288:17745-17758.
101. Civelek M., Lusis A.J. Conducting the metabolic syndrome orchestra. Nat Genet 2011, 43:506-508.
102. Fernandez-Zapico M., Molina J., Ahlquist D., et al. Functional characterization of KLF11, a novel TGFb-regulated tumor suppressor for pancreatic cancer. Pancreatology 2003, 3:436.
103. Neve B., Fernandez-Zapico M.E., Ashkenazi-Katalan V., et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci U S A 2005, 102:4807-4812.
104. Bonnefond A., Lomberk G., Buttar N., et al. Disruption of a novel Kruppel-like transcription factor p300-regulated pathway for insulin biosynthesis revealed by studies of the c.-331 INS mutation found in neonatal diabetes mellitus. J Biol Chem 2011, 286:28414-28424.
105. Stacey S.N., Sulem P., Masson G., et al. New common variants affecting susceptibility to basal cell carcinoma. Nat Genet 2009, 41:909-914.
106. Seo S., Lomberk G., Mathison A., et al. Krüppel-like factor 11 differentially couples to histone acetyltransferase and histone methyltransferase chromatin remodeling pathways to transcriptionally regulate dopamine D2 receptor in neuronal cells. J Biol Chem 2012, 287:12723-12735.
107. Lomberk G., Mathison A.J., Grzenda A., et al. Sequence-specific recruitment of heterochromatin protein 1 via interaction with Krüppel-like factor 11, a human transcription factor involved in tumor suppression and metabolic diseases. J Biol Chem 2012, 287:13026-13039.
108. Fernandez-Zapico M.E., van Velkinburgh J.C., Gutierrez-Aguilar R., et al. MODY7 gene, KLF11, is a novel p300-dependent regulator of Pdx-1 (MODY4) transcription in pancreatic islet beta cells. J Biol Chem 2009, 284:36482-36490.
109. Zhang J.-S., Moncrieffe M.C., Kaczynski J., et al. A conserved α-helical motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A. Mol Cell Biol 2001, 21:5041-5049.
110. Yin K.J., Fan Y., Hamblin M., et al. KLF11 mediates PPARgamma cerebrovascular protection in ischaemic stroke. Brain 2013, 136:1274-1287.
111. Fan Y., Guo Y., Zhang J., et al. Krüppel-like factor-11, a transcription factor involved in diabetes mellitus, suppresses endothelial cell activation via the nuclear factor-kappaB signaling pathway. Arterioscler Thromb Vasc Biol 2012, 32:2981-2988.
112. Pylayeva-Gupta Y., Grabocka E., Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web. Nat Rev Cancer 2011, 11:761-774.
113. Ayer D.E., Lawrence Q.A., Eisenman R.N. Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3. Cell 1995, 80:767-776.
114. Lomberk G., Bensi D., Fernandez-Zapico M.E., et al. Evidence for the existence of an HP1-mediated subcode within the histone code. Nat Cell Biol 2006, 8:407-415.
115. Grzenda A., Lomberk G., Svingen P., et al. Functional characterization of EZH2β reveals the increased complexity of EZH2 isoforms involved in the regulation of mammalian gene expression. Epigenetics Chromatin 2013, 6:3.