Abstract
Cancer is not a single disease, rather a group of abnormality generally associated with uncontrolled cell growth. The characteristic of a cancer is determined by its tissue of origin. In humans during the development of cancer the tumor tissue acquires several physiological abilities, termed as “Hallmarks of cancer”, through which cancer cells overcome the check point of cell cycle, avoid the immune surveillance system, disobey the growth regulatory signals and induce the assembly of new blood vessels in the tumor. Later these cells become metabolically hyperactive to harness the energy required for maintaining the various cancer hallmarks. However, apart from these cellular characteristics, physiologically cancer growth and progression is significantly dependant on the “tumor microenvironment”. All cancers are genetic but a very few are hereditary. Somatic mutations are considered to be the point of initiation. Nevertheless, the fine tuning of cancer progression, more precisely the establishment of a complex network among the genes expressed in a cancer cell is mediated by the epigenetic reprogramming, which could be affected by the tumor microenvironment (Fig. 17.1). In this chapter we shall discuss about the present understanding of the possible contribution of chromatin modifications and remodelling in cancer manifestation.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aguilera O, Fernández AF, Muñoz A, Fraga MF (2010) Epigenetics and environment: a complex relationship. J Appl Physiol 109:243–251
Arasaradnam RP, Commane DM, Bradburn D, Mathers JC (2008) A review of dietary factors and its influence on DNA methylation in colorectal carcinogenesis. Epigenetics 3:193–198
Arif M, Vedamurthy BM, Choudhari R, Ostwal YB, Mantelingu K, Kodaganur GS, Kundu TK (2010) Nitric oxide-mediated histone hyperacetylation in oral cancer: target for a water-soluble HAT inhibitor, CTK7A. Chem Biol 17:903–913
Ashktorab H, Belgrave K, Hosseinkhah F, Brim H, Nouraie M, Takkikto M, Hewitt S, Lee EL, Dashwood RH, Smoot D (2009) Global histone H4 acetylation and HDAC2 expression in colon adenoma and carcinoma. Dig Dis Sci 54:2109–2117
Ayton PM, Cleary ML (2001) Molecular mechanisms of leukemogenesis mediated by MLL fusion proteins. Oncogene 20:5695–5707
Bai X, Wu L, Liang T, Liu Z, Li J, Li D, Xie H, Yin S, Yu J, Lin Q, Zheng S (2008) Overexpression of myocyte enhancer factor 2 and histone hyperacetylation in hepatocellular carcinoma. J Cancer Res Clin Oncol 134:83–91
Balasubramanyam K, Varier RA, Altaf M, Swaminathan V, Siddappa NB, Ranga U, Kundu TK (2004) Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 279:51163–51171
Barlési F, Giaccone G, Gallegos-Ruiz MI, Loundou A, Span SW, Lefesvre P, Kruyt FA, Rodriguez JA (2007) Global histone modifications predict prognosis of resected non small-cell lung cancer. J Clin Oncol 25:4358–4364
Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6:107–116
Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA (2008) An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet 40:499–507
Bernstein BE, Mikkelsen TS, Xie X, Kamal M, Huebert DJ, Cuff J, Fry B, Meissner A, Wernig M, Plath K, Jaenisch R, Wagschal A, Feil R, Schreiber SL, Lander ES (2006) A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125:315–326
Borrelli E, Nestler EJ, Allis CD, Sassone-Corsi P (2008) Decoding the epigenetic language of neuronal plasticity. Neuron 60:961–974
Bowen NJ, Fujita N, Kajita M, Wade PA (2004) Mi-2/NuRD: multiple complexes for many purposes. Biochim Biophys Acta 1677:52–57
Chan EM, Chan RJ, Comer EM, Goulet RJ 3rd, Crean CD, Brown ZD, Fruehwald AM, Yang Z, Boswell HS, Nakshatri H, Gabig TG (2007) MOZ and MOZ-CBP cooperate with NF-kappaB to activate transcription from NF-kappaB-dependent promoters. Exp Hematol 35:1782–1792
Chuang LS, Ian HI, Koh TW, Ng HH, Xu G, Li BF (1997) Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 277:1996–2000
Conway K, Costa M (1989) Nonrandom chromosomal alterations in nickel-transformed Chinese hamster embryo cells. Cancer Res 49:6032–6038
Corfe BM, Williams EA, Bury JP, Riley SA, Croucher LJ, Lai DY, Evans CA (2009) A study protocol to investigate the relationship between dietary fibre intake and fermentation, colon cell turnover, global protein acetylation and early carcinogenesis: the FACT study. BMC Cancer 9:332
Dalvai M, Bystricky K (2010) The role of histone modifications and variants in regulating gene expression in breast cancer. J Mammary Gland Biol Neoplasia. 15(1):19–33
Das C, Lucia MS, Hansen KC, Tyler JK (2009) CBP/p300-mediated acetylation of histone H3 on lysine 56. Nature 459:113–117
Di Croce L, Raker VA, Corsaro M, Fazi F, Fanelli M, Faretta M, Fuks F, Lo Coco F, Kouzarides T, Nervi C, Minucci S, Pelicci PG (2002) Methyltransferase recruitment and DNA hypermethylation of target promoters by an oncogenic transcription factor. Science 295(5557):1079–1082
Doherty AS, Mann MR, Tremblay KD, Bartolomei MS, Schultz RM (2000) Differential effects of culture on imprinted H19 expression in the preimplantation mouse embryo. Biol Reprod 62:1526–1535
Dolinoy DC, Weidman JR, Waterland RA, Jirtle RL (2006) Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome. Environ Health Perspect 114:567–572
Dutta D, Ray S, Home P, Saha B, Wang S, Sheibani N, Tawfik O, Cheng N, Paul S (2010) Regulation of angiogenesis by histone chaperone HIRA-mediated incorporation of lysine 56-acetylated histone H3.3 at chromatin domains of endothelial genes. J Biol Chem 285:41567–41577
Elsheikh SE, Green AR, Rakha EA, Powe DG, Ahmed RA, Collins HM, Soria D, Garibaldi JM, Paish CE, Ammar AA, Grainge MJ, Ball GR, Abdelghany MK, Martinez-Pomares L, Heery DM, Ellis IO (2009) Global histone modifications in breast cancer correlate with tumor phenotypes, prognostic factors, and patient outcome. Cancer Res 69:3802–3809
Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301:89–92
Francis NJ, Kingston RE, Woodcock CL (2004) Chromatin compaction by a polycomb group protein complex. Science 306:1574–1577
Füllgrabe J, Kavanagh E, Joseph B (2011) Histone onco-modifications. Oncogene 30:3391–3403
Gibb EA, Brown CJ, Lam WL (2011) The functional role of long non-coding RNA in human carcinomas. Mol Cancer 10:38
Glaser KB, Li J, Staver MJ, Wei RQ, Albert DH, Davidsen SK (2003) Role of class I and class II histone deacetylases in carcinoma cells using siRNA. Biochem Biophys Res Commun 310:529–536
Govindarajan B, Klafter R, Miller MS, Mansur C, Mizesko M, Bai X, LaMontagne K Jr, Arbiser JL (2002) Reactive oxygen-induced carcinogenesis causes hypermethylation of p16(Ink4a) and activation of MAP kinase. Mol Med 8:1–8
Hamid A, Kiran M, Rana S, Kaur J (2009) Low folate transport across intestinal basolateral surface is associated with down-regulation of reduced folate carrier in in vivo model of folate malabsorption. IUBMB Life 61:236–243
Hansen KH, Bracken AP, Pasini D, Dietrich N, Gehani SS, Monrad A, Rappsilber J, Lerdrup M, Helin K (2008) A model for transmission of the H3K27me3 epigenetic mark. Nat Cell Biol 10:1291–1300
Hargreaves DC, Crabtree GR (2011) ATP-dependent chromatin remodeling: genetics, genomics and mechanisms. Cell Res 21(3):396–420
Hatziapostolou M, Iliopoulos D (2011) Epigenetic aberrations during oncogenesis. Cell Mol Life Sci 68:1681–1702
He L, Hannon GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5:522–531
Henikoff S, Furuyama T (2010) Epigenetic inheritance of centromeres. Cold Spring Harb Symp Quant Biol 75:51–60
Hitchler MJ, Domann FE (2009) Metabolic defects provide a spark for the epigenetic switch in cancer. Free Radic Biol Med 47:115–127
Hobo W, Maas F, Adisty N, de Witte T, Schaap N, van der Voort R, Dolstra H (2010) siRNA silencing of PD-L1 and PD-L2 on dendritic cells augments expansion and function of minor histocompatibility antigen-specific CD8+ T cells. Blood 116:4501–4511
Hughes LA, van den Brandt PA, de Bruïne AP, Wouters KA, Hulsmans S, Spiertz A, Goldbohm RA, de Goeij AF, Herman JG, Weijenberg MP, van Engeland M (2009) Early life exposure to famine and colorectal cancer risk: a role for epigenetic mechanisms. PLoS One 4:e7951
Ida K, Kitabayashi I, Taki T, Taniwaki M, Noro K, Yamamoto M, Ohki M, Hayashi Y (1997) Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;q13). Blood 90:4699–4704
Issa JP, Vertino PM, Boehm CD, Newsham IF, Baylin SB (1996) Switch from monoallelic to biallelic human IGF2 promoter methylation during aging and carcinogenesis. Proc Natl Acad Sci U S A 93:11757–11762
Kalantari M, Calleja-Macias IE, Tewari D, Hagmar B, Lie K, Barrera-Saldana HA, Wiley DJ, Bernard HU (2004) Conserved methylation patterns of human papillomavirus type 16 DNA in asymptomatic infection and cervical neoplasia. J Virol 78:12762–12772
Kapoor-Vazirani P, Kagey JD, Powell DR, Vertino PM (2008) Role of hMOF-dependent histone H4 lysine 16 acetylation in the maintenance of TMS1/ASC gene activity. Cancer Res 68:6810–6821
Keku T, Millikan R, Worley K, Winkel S, Eaton A, Biscocho L, Martin C, Sandler R (2002) 5,10-Methylenetetrahydrofolate reductase codon 677 and 1298 polymorphisms and colon cancer in African Americans and whites. Cancer Epidemiol Biomarkers Prev 11:1611–1621
Khare SP, Sharma A, Deodhar KK, Gupta S (2011) Overexpression of histone variant H2A.1 and cellular transformation are related in N-nitrosodiethylamine-induced sequential hepatocarcinogenesis. Exp Biol Med (Maywood) 236:30–35
Klein CB, Conway K, Wang XW, Bhamra RK, Lin XH, Cohen MD, Annab L, Barrett JC, Costa M (1991) Senescence of nickel-transformed cells by an X chromosome: possible epigenetic control. Science 251:796–799
Knox SS (2010) From ‘omics’ to complex disease: a systems biology approach to gene-environment interactions in cancer. Cancer Cell Int 10:11
Kunert N, Wagner E, Murawska M, Klinker H, Kremmer E, Brehm A (2009) dMec: a novel Mi-2 chromatin remodelling complex involved in transcriptional repression. EMBO J 28:533–544
Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, Wiggins JF, Bader AG, Fagin R, Brown D, Tang DG (2011) The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat Med 17:211–215
Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, Sweet-Cordero A, Ebert BL, Mak RH, Ferrando AA, Downing JR, Jacks T, Horvitz HR, Golub TR (2005) MicroRNA expression profiles classify human cancers. Nature 435:834–838
Maekita T, Nakazawa K, Mihara M, Nakajima T, Yanaoka K, Iguchi M, Arii K, Kaneda A, Tsukamoto T, Tatematsu M, Tamura G, Saito D, Sugimura T, Ichinose M, Ushijima T (2006) High levels of aberrant DNA methylation in Helicobacter pylori-infected gastric mucosae and its possible association with gastric cancer risk. Clin Cancer Res 12:989–995
Marquardt JU, Factor VM, Thorgeirsson SS (2010) Epigenetic regulation of cancer stem cells in liver cancer: current concepts and clinical implications. J Hepatol 53:568–577
Martinez-Outschoorn UE, Prisco M, Ertel A, Tsirigos A, Lin Z, Pavlides S, Wang C, Flomenberg N, Knudsen ES, Howell A, Pestell RG, Sotgia F, Lisanti MP (2011) Ketones and lactate increase cancer cell “stemness,” driving recurrence, metastasis and poor clinical outcome in breast cancer: achieving personalized medicine via Metabolo-Genomics. Cell Cycle 10:1271–1286
Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S, Jackson SP (2010) Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 17:1144–1151
Mills AA (2010) Throwing the cancer switch: reciprocal roles of polycomb and trithorax proteins. Nat Rev Cancer 10:669–682
Morimoto T, Sunagawa Y, Kawamura T, Takaya T, Wada H, Nagasawa A, Komeda M, Fujita M, Shimatsu A, Kita T, Hasegawa K (2008) The dietary compound curcumin inhibits p300 histone acetyltransferase activity and prevents heart failure in rats. J Clin Invest 118:868–878
Morrish F, Noonan J, Perez-Olsen C, Gafken PR, Fitzgibbon M, Kelleher J, VanGilst M, Hockenbery D (2010) Myc-dependent mitochondrial generation of acetyl-CoA contributes to fatty acid biosynthesis and histone acetylation during cell cycle entry. J Biol Chem 285:36267–36274
Morrison AJ, Shen X (2009) Chromatin remodelling beyond transcription: the INO80 and SWR1 complexes. Nat Rev Mol Cell Biol 10:373–384
Novikov L, Park JW, Chen H, Klerman H, Jalloh AS, Gamble MJ (2011) QKI-mediated alternative splicing of the histone variant MacroH2A1 regulates cancer cell proliferation. Mol Cell Biol 31:4244–4255
Olaharski AJ, Rine J, Marshall BL, Babiarz J, Zhang L, Verdin E, Smith MT (2005) The flavoring agent dihydrocoumarin reverses epigenetic silencing and inhibits sirtuin deacetylases. PLoS Genet 1:e77
Oommen AM, Griffin JB, Sarath G, Zempleni J (2005) Roles for nutrients in epigenetic events. J Nutr Biochem 16:74–77
Peter ME (2009) Let-7 and miR-200 microRNAs: guardians against pluripotency and cancer progression. Cell Cycle 8:843–852
Piestrzeniewicz-Ulanska D, Brys M, Semczuk A, Rechberger T, Jakowicki JA, Krajewska WM (2004) TGF-beta signaling is disrupted in endometrioid-type endometrial carcinomas. Gynecol Oncol 95:173–180
Pucci S, Mazzarelli P (2011) MicroRNA dysregulation in colon cancer microenvironment interactions: the importance of small things in metastases. Cancer Microenviron 4:155–162
Ringrose L, Ehret H, Paro R (2004) Distinct contributions of histone H3 lysine 9 and 27 methylation to locus-specific stability of polycomb complexes. Mol Cell 16:641–653
Robertson KD, Jones PA (2000) DNA methylation: past, present and future directions. Carcinogenesis 21:461–467
Ryan JL, Jones RJ, Kenney SC, Rivenbark AG, Tang W, Knight ER, Coleman WB, Gulley ML (2010) Epstein-Barr virus-specific methylation of human genes in gastric cancer cells. Infect Agent Cancer 5:27
Salnikow K, Zhitkovich A (2008) Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21:28–44
Santisteban MS, Hang M, Smith MM (2011) Histone variant H2A.Z and RNA polymerase II transcription elongation. Mol Cell Biol 31:1848–1860
Seligson DB, Horvath S, Shi T, Yu H, Tze S, Grunstein M, Kurdistani SK (2005) Global histone modification patterns predict risk of prostate cancer recurrence. Nature 435:1262–1266
Sharma S, Kelly TK, Jones PA (2010) Epigenetics in cancer. Carcinogenesis 31:27–36
Siddiqi S, Matushansky I (2011) Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem. doi:10.1002/jcb.23363
Sporn JC, Kustatscher G, Hothorn T, Collado M, Serrano M, Muley T, Schnabel P, Ladurner AG (2009) Histone macroH2A isoforms predict the risk of lung cancer recurrence. Oncogene 28(38):3423–3428
Sutherland JE, Peng W, Zhang Q, Costa M (2001) The histone deacetylase inhibitor trichostatin A reduces nickel-induced gene silencing in yeast and mammalian cells. Mutat Res 479:225–233
Sykes SM, Mellert HS, Holbert MA, Li K, Marmorstein R, Lane WS, McMahon SB (2006) Acetylation of the p53 DNA-binding domain regulates apoptosis induction. Mol Cell 24:841–851
Tjeertes JV, Miller KM, Jackson SP (2009) Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28:1878–1889
Tomonaga T, Matsushita K, Ishibashi M, Nezu M, Shimada H, Ochiai T, Yoda K, Nomura F (2005) Centromere protein H is up-regulated in primary human colorectal cancer and its overexpression induces aneuploidy. Cancer Res 65(11):4683–4689
Tong ZT, Cai MY, Wang XG, Kong LL, Mai SJ, Liu YH, Zhang HB, Liao YJ, Zheng F, Zhu W, Liu TH, Bian XW, Guan XY, Lin MC, Zeng MS, Zeng YX, Kung HF, Xie D (2011) EZH2 supports nasopharyngeal carcinoma cell aggressiveness by forming a co-repressor complex with HDAC1/HDAC2 and snail to inhibit E-cadherin. Oncogene. doi:10.1038/onc.2011.254
Tsai MC, Manor O, Wan Y, Mosammaparast N, Wang JK, Lan F, Shi Y, Segal E, Chang HY (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329:689–693
Tsukuda T, Fleming AB, Nickoloff JA, Osley MA (2005) Chromatin remodelling at a DNA double-strand break site in Saccharomyces cerevisiae. Nature 438(7066):379–383
Valeri N, Vannini I, Fanini F, Calore F, Adair B, Fabbri M (2009) Epigenetics, miRNAs, and human cancer: a new chapter in human gene regulation. Mamm Genome 20:573–580
Van Den Broeck A, Brambilla E, Moro-Sibilot D, Lantuejoul S, Brambilla C, Eymin B, Khochbin S, Gazzeri S (2008) Loss of histone H4K20 trimethylation occurs in preneoplasia and influences prognosis of non-small cell lung cancer. Clin Cancer Res 14:7237–7245
Vempati RK, Jayani RS, Notani D, Sengupta A, Galande S, Haldar D (2010) p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals. J Biol Chem 285:28553–28564
Versteege I, Sévenet N, Lange J, Rousseau-Merck MF, Ambros P, Handgretinger R, Aurias A, Delattre O (1998) Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 394(6689):203–206
Warburg O (1956) On respiratory impairment in cancer cells. Science 124:269–270
Waterland RA (2006) Assessing the effects of high methionine intake on DNA methylation. J Nutr 136:1706S–1710S
Wei Y, Xia W, Zhang Z, Liu J, Wang H, Adsay NV, Albarracin C, Yu D, Abbruzzese JL, Mills GB, Bast RC Jr, Hortobagyi GN, Hung MC (2008) Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers. Mol Carcinog 47:701–706
Wellen KE, Hatzivassiliou G, Sachdeva UM, Bui TV, Cross JR, Thompson CB (2009) ATP-citrate lyase links cellular metabolism to histone acetylation. Science 324:1076–1080
Widschwendter M, Fiegl H, Egle D, Mueller-Holzner E, Spizzo G, Marth C, Weisenberger DJ, Campan M, Young J, Jacobs I, Laird PW (2007) Epigenetic stem cell signature in cancer. Nat Genet 39:157–158
Wilson BG, Roberts CW (2011) SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 11:481–492
Witt O, Deubzer HE, Milde T, Oehme I (2009) HDAC family: what are the cancer relevant targets? Cancer Lett 277:8–21
Wu G, Bazer FW, Cudd TA, Meininger CJ, Spencer TE (2004) Maternal nutrition and fetal development. J Nutr 134:2169–2172
Xiang Y, Zhu Z, Han G, Lin H, Xu L, Chen CD (2007) JMJD3 is a histone H3K27 demethylase. Cell Res 17:850–857
Yu J, Yu J, Rhodes DR, Tomlins SA, Cao X, Chen G, Mehra R, Wang X, Ghosh D, Shah RB, Varambally S, Pienta KJ, Chinnaiyan AM (2007) A polycomb repression signature in metastatic prostate cancer predicts cancer outcome. Cancer Res 67:10657–10663
Yuan J, Pu M, Zhang Z, Lou Z (2009) Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8:1747–1753
Zeisel SH (2007) Gene response elements, genetic polymorphisms and epigenetics influence the human dietary requirement for choline. IUBMB Life 59:380–387
Zhao CQ, Young MR, Diwan BA, Coogan TP, Waalkes MP (1997) Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression. Proc Natl Acad Sci U S A 94:10907–10912
Zimmermann S, Kiefer F, Prudenziati M, Spiller C, Hansen J, Floss T, Wurst W, Minucci S, Göttlicher M (2007) Reduced body size and decreased intestinal tumor rates in HDAC2-mutant mice. Cancer Res 67:9047–9054
Acknowledgments
Work done in our laboratory is supported by Department of Biotechnology, Govt. of India; Department of Science and Technology (DST), Govt. of India, and Jawaharlal Nehru Centre for Advanced Scientific Research. TKK is a recipient of Sir JC Bose fellowship (DST). DK and MA are senior research fellows of the Council of Scientific and Industrial Research (CSIR), India.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Dhanasekaran, K., Arif, M., Kundu, T.K. (2013). Cancer: An Epigenetic Landscape. In: Kundu, T. (eds) Epigenetics: Development and Disease. Subcellular Biochemistry, vol 61. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4525-4_17
Download citation
DOI: https://doi.org/10.1007/978-94-007-4525-4_17
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-4524-7
Online ISBN: 978-94-007-4525-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)