Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-8448b6f56d-xtgtn Total loading time: 0 Render date: 2024-04-18T08:16:58.391Z Has data issue: false hasContentIssue false

8 - Metastasis Genes: Epigenetics

from GENES

Published online by Cambridge University Press:  05 June 2012

By
Amaia Lujambio  and
Manel Esteller
Edited by
David Lyden ,
Danny R. Welch  and
Bethan Psaila
Amaia Lujambio
Affiliation:
Catalan Institute of Oncology, Spain
Manel Esteller
Affiliation:
Catalan Institute of Oncology, Spain
David Lyden
Affiliation:
Weill Cornell Medical College, New York
Danny R. Welch
Affiliation:
Weill Cornell Medical College, New York
Bethan Psaila
Affiliation:
Imperial College of Medicine, London
Get access

Summary

Metastasis is the sequence of interrelated steps by which primary tumor cells acquire the capability to invade adjacent tissue, enter the systemic circulation (intravasate), translocate through the vasculature, arrest in distant capillaries, extravasate into the surrounding tissue parenchyma, and, finally, proliferate from micrometastases into macroscopic secondary tumors [1, 2]. This metastatic process is the cause of 90 percent of deaths in patients with solid tumors [1, 2]. Therefore, unraveling the inner mechanisms of the pathogenesis of metastasis at systemic, cellular, and molecular levels has become a major goal of cancer research [1, 2].

In recent years, the contribution of epigenetics to the field of cancer has been of paramount importance, because cancer is both a genetic and an epigenetic disease [3] and because epigenetic alterations are also involved in the metastatic process [4]. Thus, cancer cells have to gain an epigenotype to disseminate from the primary tumor mass or to survive and proliferate at a secondary tissue site [4].

We are still in the early stages of deciphering the timing and hierarchy of these epigenetic lesions; we need to know how epigenetic mechanisms operate in normal and cancer cells to understand the epigenetic changes that occur in metastasis. This information will allow us to identify new metastasis-related genes, to discover new epigenetic biomarkers that may help identify the diagnostic signatures of metastasis, and to develop new cancer therapies based on epigenetic drugs [5].

Type
Chapter
Information
Cancer Metastasis
Biologic Basis and Therapeutics
 , pp. 85 - 95
Publisher: Cambridge University Press
Print publication year: 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Fidler, IJ (2003) The pathogenesis of cancer metastasis: the “seed and soil” hypothesis revisited. Nature Rev Cancer. 3: 453–458.CrossRefGoogle Scholar
Gupta, GP, Massague, J (2006) Cancer metastasis: building a framework. Cell. 127: 679–695.CrossRefGoogle ScholarPubMed
Esteller, M (2008) Epigenetics in cancer. N Engl J Med. 358: 1148–1159.CrossRefGoogle Scholar
Rodenhiser, DI (2009) Epigenetic contributions to cancer metastasis. Clin Exp Metastasis. 26: 5–18. Epub ahead of print.CrossRefGoogle ScholarPubMed
Chambers, AF, Groom, AC, MacDonald, IC (2002) Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2: 563–572.CrossRefGoogle ScholarPubMed
Egger, G, Liang, G, Aparicio, A, Jones, PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature. 429: 457–463.CrossRefGoogle ScholarPubMed
Jones, PA, Laird, PW (1999) Cancer epigenetics comes of age. Nat Genet. 21: 163–167.CrossRefGoogle ScholarPubMed
Esteller, M (2005) Aberrant DNA methylation as a cancerinducing mechanism. Annu Rev Pharmacol Toxicol. 45: 629–656.CrossRefGoogle ScholarPubMed
Kaneda, M, Okano, M, Hata, K et al. (2004) Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 429: 900–903.CrossRefGoogle Scholar
Klose, RJ, Bird, AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci. 31: 89–97.CrossRefGoogle ScholarPubMed
Takai, D, Jones, PA (2002) Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A 99: 3740–3745.CrossRefGoogle ScholarPubMed
Takai, D, Jones, PA (2003) The CpG island searcher: a new WWW resource. In Silico Biol. 3: 235–240.Google ScholarPubMed
Esteller, M (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat Rev Genet. 4: 286–298.CrossRefGoogle Scholar
Csankovszki, G, Nagy, A, Jaenisch, R (2001) Synergism of Xist RNA, DNA methylation, and histone hypoacetylation in maintaining X chromosome inactivation. J Cell Biol. 153: 773–784.CrossRefGoogle ScholarPubMed
Walsh, CP, Chaillet, JR, Bestor, TH (1998) Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nat Genet. 20: 116–117.CrossRefGoogle ScholarPubMed
Bodey, B (2002) Cancer-testis antigens: promising targets for antigen directed antineoplastic immunotherapy. Expert Opin Biol Ther. 2: 577–584.CrossRefGoogle ScholarPubMed
Futscher, BW, Oshiro, MM, Wozniak, RJ et al. (2002) Role for DNA methylation in the control of cell type specific maspin expression. Nat Genet. 31: 175–179.CrossRefGoogle ScholarPubMed
Wang, Y, Fischle, W, Cheung, W, Jacobs, S, Khorasanizadeh, S, Allis, CD (2004) Beyond the double helix: writing and reading the histone code. Novartis Found Symp. 259: 3–17.Google ScholarPubMed
Peters, AH, Mermoud, JE, O'Carroll, D (2002) Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet. 30: 77–80.CrossRefGoogle ScholarPubMed
Sanders, SL, Portoso, M, Mata, J, Bähler, J, Allshire, RC, Kouzarides, T (2004) Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell. 119: 603–614.CrossRefGoogle ScholarPubMed
Ballestar, E, Esteller, M (2002) The impact of chromatin in human cancer: linking DNA methylation to gene silencing. Carcinogenesis. 23: 1103–1109.CrossRefGoogle ScholarPubMed
Esteller, M (2006) Epigenetics provides a new generation of oncogenes and tumor-suppressor genes. Br J Cancer. 94: 179–83.CrossRefGoogle Scholar
Welch, DR (2004) Microarrays bring new insights into understanding of breast cancer metastasis to bone. Breast Cancer Res. 6: 61–64.CrossRefGoogle ScholarPubMed
Hanahan, D, Weinberg, RA (2000) The hallmarks of cancer. Cell. 100: 57–70.CrossRefGoogle ScholarPubMed
Bernstein, BE, Meissner, A, Lander, ES (2007) The mammalian epigenome. Cell. 128: 669–681.CrossRefGoogle ScholarPubMed
Jones, PA, Baylin, SB (2007) The epigenomics of cancer. Cell. 128: 683–692.CrossRefGoogle Scholar
Kouzarides, T (2007) Chromatin modifications and their function. Cell. 128: 693–705.CrossRefGoogle ScholarPubMed
Herman, JG, Baylin, SB (2003) Gene silencing in cancer in association with promoter hypermethylation. N Eng J Med. 349: 2042–2054.CrossRefGoogle ScholarPubMed
Feinberg, AP, Vogelstein, B (1983). Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 301: 89–92.CrossRefGoogle ScholarPubMed
Fraga, MF, Herranz, M, Espada, J et al. (2004) A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res. 64: 5527–5534.CrossRefGoogle ScholarPubMed
Fraga, MF, Rodríguez, R, Canal, MJ (2000) Rapid quantification of DNA methylation by high performance capillary electrophoresis. Electrophoresis. 21: 2990–2994.3.0.CO;2-I>CrossRefGoogle ScholarPubMed
Fraga, MF, Uriel, E, Borja, Diego L et al. (2002) High-performance capillary electrophoretic method for the quantification of 5-methyl 2′-deoxycytidine in genomic DNA: application to plant, animal and human cancer tissues. Electrophoresis 23: 1677–1681.3.0.CO;2-Z>CrossRefGoogle ScholarPubMed
Paz, MF, Fraga, MF, Avila, S et al. (2003) A systematic profile of DNA methylation in human cancer cell lines. Cancer Res. 63: 1114–1121.Google ScholarPubMed
Habib, M, Fares, F, Bourgeois, CA et al. (1999) DNA global hypomethylation in EBV-transformed interphase nuclei. Exp Cell Res. 249: 46–53.CrossRefGoogle ScholarPubMed
Eden, A, Gaudet, F, Waghmare, A, Jaenisch, R (2003) Chromosomal instability and tumors promoted by DNA hypomethylation. Science. 300: 455.CrossRefGoogle ScholarPubMed
Karpf, AR, Matsui, S (2005) Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells. Cancer Res. 65: 8635–8639.CrossRefGoogle ScholarPubMed
Cui, H, Cruz-Correa, M, Giardiello, FM et al. (2003) Loss of IGF2 imprinting: a potential marker of colorectal cancer risk. Science. 299: 1753–1755.CrossRefGoogle ScholarPubMed
Kaneda, A, Feinberg, AP (2005) Loss of imprinting of IGF2: a common epigenetic modifier of intestinal tumor risk. Cancer Res. 65: 11236–11240.CrossRefGoogle ScholarPubMed
Feinberg, AP (1999) Imprinting of a genomic domain of 11p15 and loss of imprinting in cancer: an introduction. Cancer Res. 59: Suppl:1743s–1746s.Google Scholar
Xu, GL, Bestor, TH, Bourc'his, D et al. (1999) Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature. 402: 187–191.CrossRefGoogle Scholar
Choi, IS, Estecio, MR, Nagano, Y et al. (2007) Hypomethylation of LINE-1 and Alu in well-differentiated neuroendocrine tumors (pancreatic endocrine tumors and carcinoid tumors). Mod Pathol. 20: 802–810.CrossRefGoogle ScholarPubMed
Schulz, WA, Elo, JP, Florl, AR et al. (2002) Genomewide DNA hypomethylation is associated with alterations on chromosome 8 in prostate carcinoma. Genes Chromosomes Cancer. 35: 58–65.CrossRefGoogle ScholarPubMed
Feinberg, AP, Tycko, B (2004) The history of cancer epigenetics. Nat Rev Cancer. 4: 143–153.CrossRefGoogle ScholarPubMed
Wu, H, Chen, Y, Liang, J et al. (2005) Hypomethylation-linked activation of PAX2 mediates tamoxifen-stimulated endometrial carcinogenesis. Nature. 438: 981–987.CrossRefGoogle ScholarPubMed
Brueckner, B, Stresemann, C, Kuner, R et al. (2007) The human let-7a-3 locus contains an epigenetically regulated microRNA gene with oncogenic function. Cancer Res. 67: 1419–1423.CrossRefGoogle ScholarPubMed
Nakamura, N, Takenaga, K (1998) Hypomethylation of the metastasis-associated S100A4 gene correlates with gene activation in human colon adenocarcinoma cell lines. Clin Exp Metastasis. 16: 471–479.CrossRefGoogle ScholarPubMed
Lindsey, JC, Lusher, ME, Anderton, JA, Gilbertson, RJ, Ellison, DW, Clifford, SC (2007) Epigenetic deregulation of multiple S100 gene family members by differential hypomethylation and hypermethylation events in medulloblastoma. Br J Cancer. 97: 267–274.CrossRefGoogle ScholarPubMed
Rosty, C, Ueki, T, Argani, P et al. (2002) Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am J Pathol. 160: 45–50.CrossRefGoogle ScholarPubMed
Xie, R, Loose, DS, Shipley, GL, Xie, S, Bassett, RL Jr, Broaddus, RR (2007) Hypomethylation-induced expression of S100A4 in endometrial carcinoma. Mod Pathol. 20: 1045–1054.CrossRefGoogle ScholarPubMed
Pakneshan, P, Szyf, M, Farias-Eisner, R et al. (2004) Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis. J Biol Chem. 279: 31735–31744.CrossRefGoogle ScholarPubMed
Gupta, A, Godwin, AK, Vanderveer, L, Lu, A, Liu, J (2003) Hypomethylation of the synuclein gamma gene CpG island promotes its aberrant expression in breast carcinoma and ovarian carcinoma. Cancer Res. 63: 664–673.Google ScholarPubMed
Ballestar, E, Paz, MF, Valle, L et al. (2003) Methyl-CpG binding proteins identify novel sites of epigenetic inactivation in human cancer. EMBO J. 22: 6335–6345.CrossRefGoogle ScholarPubMed
Richon, VM, Sandhoff, TW, Rifkind, RA, Marks, PA (2000) Histone deacetylase inhibitor selectively induces p21WAF1 expression and gene-associated histone acetylation. Proc Natl Acad Sci USA. 97: 10014–10019.CrossRefGoogle ScholarPubMed
Mack, GS (2006) Epigenetic cancer therapy makes headway. J Natl Cancer Inst. 98: 1443–1444.CrossRefGoogle ScholarPubMed
Fraga, MF, Ballestar, E, Villar-Garea, A et al. (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet. 37: 391–400.CrossRefGoogle ScholarPubMed
Pogribny, IP, Ross, SA, Tryndyak, VP, Pogribna, M, Poirier, , Karpinets, TV (2006) Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of Suv4–20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis induced by methyl deficiency in rats. Carcinogenesis. 27: 1180–1186.CrossRefGoogle ScholarPubMed
Tryndyak, VP, Kovalchuk, O, Pogribny, IP (2006) Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4–20h2 histone methyltransferase and methyl-binding proteins. Cancer Biol Ther. 5: 65–70.CrossRefGoogle ScholarPubMed
Greger, V, Passarge, E, Höpping, W, Messmer, E, Horsthemke, B (1989) Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 83: 155–158.CrossRefGoogle ScholarPubMed
Sakai, T, Toguchida, J, Ohtani, N, Yandell, DW, Rapaport, JM, Dryja, TP (1991) Allele-specific hypermethylation of the retinoblastoma tumor-suppressor gene. Am Hum Genet. 48: 880–888.Google ScholarPubMed
Herman, JG, Latif, F, Weng, Y et al. (1994) Silencing of the VHL tumor-suppressor gene by DNA methylation in renal carcinoma. Proc Natl Acad Sci USA. 91: 9700–9704.CrossRefGoogle ScholarPubMed
Merlo, A, Herman, JG, Mao, L et al. (1995) 5′ CpG island methylation is associated with transcriptional silencing of the tumor suppressor p16/CDKN2/MTS1 in human cancers. Nat Med. 1: 686–692.CrossRefGoogle ScholarPubMed
Herman, JG, Merlo, A, Mao, L et al. (1995) Inactivation of the CDKN2/p16/MTS1 gene is frequently associated with aberrant DNA methylation in all common human cancers. Cancer Res. 55: 4525–4530.Google ScholarPubMed
Gonzalez-Zulueta, M, Bender, CM, Yang, AS et al. (1995) Methylation of the 5′ CpG island of the p16/CDKN2 tumor suppressor gene in normal and transformed human tissues correlates with gene silencing. Cancer Res. 55: 4531–4535.Google ScholarPubMed
Esteller, M, Silva, JM, Dominguez, G et al. (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst. 92: 564–569.CrossRefGoogle ScholarPubMed
Graff, JR, Herman, JG, Lapidus, RG et al. (1995) E-cadherin expression is silenced by DNA hypermethylation in human breast and prostate carcinomas. Cancer Res. 55: 5195–5199.Google ScholarPubMed
Yoshiura, K, Kanai, Y, Ochiai, A, Shimoyama, Y, Sugimura, T, Hirohashi, S (1995) Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas. Proc Natl Acad Sci U S A 92: 7416–7419.CrossRefGoogle ScholarPubMed
Graff, JR, Gabrielson, E, Fujii, H, Baylin, SB, Herman, JG (2000) Methylation patterns of the E-cadherin 5′ CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression. J Biol Chem. 275: 2727–2732.CrossRefGoogle ScholarPubMed
Bolós, V, Peinado, H, Pérez-Moreno, MA, Fraga, MF, Esteller, M, Cano, A (2003) The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J Cell Sci. 116(Pt 3): 499–511.CrossRefGoogle ScholarPubMed
Peinado, H, Ballestar, E, Esteller, M, Cano, A (2004) Snail mediates E-cadherin repression by the recruitment of the Sin3A/histone deacetylase 1 (HDAC1)/HDAC2 complex. Mol Cell Biol. 24: 306–319.CrossRefGoogle ScholarPubMed
Sato, M, Mori, Y, Sakurada, A, Fujimura, S, Horii, A (1998) The H-cadherin (CDH13) gene is inactivated in human lung cancer. Hum Genet. 103: 96–101.CrossRefGoogle ScholarPubMed
Toyooka, KO, Toyooka, S, Virmani, AK et al. (2001) Loss of expression and aberrant methylation of the CDH13 (H-cadherin) gene in breast and lung carcinomas. Cancer Res 61: 4556–4560.Google ScholarPubMed
Miotto, E, Sabbioni, S, Veronese, A et al. (2004) Frequent aberrant methylation of the CDH4 gene promoter in human colorectal and gastric cancer. Cancer Res 64: 8156–8159.CrossRefGoogle ScholarPubMed
Paz, MF, Wei, S, Cigudosa, JC et al. (2003) Genetic unmasking of epigenetically silenced tumor suppressor genes in colon cancer cells deficient in DNA methyltransferases. Hum Mol Genet. 12: 2209–2219.CrossRefGoogle ScholarPubMed
Ropero, S, Setien, F, Espada, J et al. (2004) Epigenetic loss of the familial tumor-suppressor gene exostosin-1 (EXT1) disrupts heparan sulfate synthesis in cancer cells. Hum Mol Genet. 13: 2753–2765.CrossRefGoogle ScholarPubMed
Lin, H, Huber, R, Schlessinger, D, Morin, PJ (1999) Frequent silencing of the GPC3 gene in ovarian cancer cell lines. Cancer Res. 59: 807–810.Google ScholarPubMed
Miyamoto, K, Asada, K, Fukutomi, T et al. (2003) Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers. Oncogene. 22: 274–280.CrossRefGoogle ScholarPubMed
Overall, CM, Kleifeld, O (2006) Tumour microenvironment – opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 6: 227–239.CrossRefGoogle ScholarPubMed
Esteller, M, Fraga, MF, Guo, M et al. (2001) DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis. Hum Mol Genet. 10: 3001–3007.CrossRefGoogle ScholarPubMed
Bachman, KE, Herman, JG, Corn, PG et al. (1999) Methylation-associated silencing of the tissue inhibitor of metalloproteinase-3 gene suggests a suppressor role in kidney, brain, and other human cancers. Cancer Res. 59: 798–802.Google Scholar
Ivanova, T, Vinokurova, S, Petrenko, A et al. (2004) Frequent hypermethylation of 5′ flanking region of TIMP-2 gene in cervical cancer. Int J Cancer. 108: 882–886.CrossRefGoogle ScholarPubMed
Galm, O, Suzuki, H, Akiyama, Y et al. (2005) Inactivation of the tissue inhibitor of metalloproteinases-2 gene by promoter hypermethylation in lymphoid malignancies. Oncogene. 24: 4799–4805.CrossRefGoogle ScholarPubMed
Pulukuri, SM, Patibandla, S, Patel, J, Estes, N, Rao, JS (2007) Epigenetic inactivation of the tissue inhibitor of metalloproteinase-2 (TIMP-2) gene in human prostate tumors. Oncogene. 26: 5229–5237.CrossRefGoogle ScholarPubMed
Konduri, SD, Srivenugopal, KS, Yanamandra, N, Dinh, DH, Olivero, WC, Gujrati, M, Foster, DC, Kisiel, W, Ali-Osman, F, Kondraganti, S, Lakka, SS, Rao, JS (2003) Promoter methylation and silencing of the tissue factor pathway inhibitor-2 (TFPI-2), a gene encoding an inhibitor of matrix metalloproteinases in human glioma cells. Oncogene 22: 4509–4516.CrossRefGoogle Scholar
Sato, N, Parker, AR, Fukushima, N et al. (2005) Epigenetic inactivation of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma. Oncogene. 24: 850–858.CrossRefGoogle ScholarPubMed
Suzuki, K, Kumanogoh, A, Kikutani, H (2008) Semaphorins and their receptors in immune cell interactions. Nat Immunol. 9: 17–23.CrossRefGoogle ScholarPubMed
Ji, L, Minna, JD, Roth, JA (2005) 3p21.3 tumor suppressor cluster: prospects for translational applications. Future Oncol. 1: 79–92.CrossRefGoogle ScholarPubMed
Tomizawa, Y, Sekido, Y, Kondo, M et al. (2001) Inhibition of lung cancer cell growth and induction of apoptosis after reexpression of 3p21.3 candidate tumor suppressor gene SEMA3B. Proc Natl Acad Sci U S A 98: 13954–13959.CrossRefGoogle ScholarPubMed
Kuroki, T, Trapasso, F, Yendamuri, S et al. (2003) Allelic loss on chromosome 3p21.3 and promoter hypermethylation of semaphorin 3B in non-small cell lung cancer. Cancer Res. 63: 3352–3355.Google ScholarPubMed
Dickinson, RE, Dallol, A, Bieche, I et al. (2004) Epigenetic inactivation of SLIT3 and SLIT1 genes in human cancers. Br J Cancer. 91: 2071–2078.CrossRefGoogle ScholarPubMed
Kazerounian, S, Yee, KO, Lawler, J (2008) Thrombospondins in cancer. Cell Mol Life Sci. 65: 700–712.CrossRefGoogle Scholar
Lawler, J, Detmar, M (2004) Tumor progression: the effects of thrombospondin-1 and -2. Int J Biochem Cell Biol. 36: 1038–1045.CrossRefGoogle ScholarPubMed
Li, Q, Ahuja, N, Burger, PC, Issa, JP (1999) Methylation and silencing of the thrombospondin-1 promoter in human cancer. Oncogene. 18: 3284–3289.CrossRefGoogle ScholarPubMed
Schéele, S, Nyström, A, Durbeej, M, Talts, JF, Ekblom, M, Ekblom, P (2007) Laminin isoforms in development and disease. J Mol Med. 85: 825–836.CrossRefGoogle ScholarPubMed
Sathyanarayana, UG, Toyooka, S, Padar, A et al. (2003) Epigenetic inactivation of laminin-5-encoding genes in lung cancers. Clin Cancer Res. 9: 2665–2672.Google ScholarPubMed
He, L, Hannon, GJ (2004) MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 5: 522–531.CrossRefGoogle ScholarPubMed
Lu, J, Getz, G, Miska, EA et al. (2005) MicroRNA expression profiles classify human cancers. Nature. 435: 834–838.CrossRefGoogle ScholarPubMed
Calin, GA, Dumitru, CD, Shimizu, M et al. (2002) Frequent deletions and downregulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci U S A 99: 15524–15529.CrossRefGoogle ScholarPubMed
Takamizawa, J, Konishi, H, Yanagisawa, K et al. (2004) Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 64: 3753–3756.CrossRefGoogle ScholarPubMed
Cimmino, A, Calin, GA, Fabbri, M et al. (2005) miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc Natl Acad Sci U S A 102: 13944–13949.CrossRefGoogle ScholarPubMed
Johnson, SM, Grosshans, H, Shingara, J et al. (2005) RAS is regulated by the let-7 MicroRNA family. Cell. 120: 635–647.CrossRefGoogle ScholarPubMed
Hammond, SM (2006) MicroRNAs as oncogenes. Curr Opin Genet Dev. 16: 4–9.CrossRefGoogle ScholarPubMed
Chan, JA, Krichevsky, AM, Kosik, KS (2005) MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 65: 6029–6033.CrossRefGoogle ScholarPubMed
He, L, Thomson, JM, Hemann, MT et al. (2005) A microRNA polycistron as a potential human oncogene. Nature. 435: 828–833.CrossRefGoogle ScholarPubMed
Ma, L, Teruya-Feldstein, J, Weinberg, RA (2007) Tumor invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 449: 682–688.CrossRefGoogle ScholarPubMed
Huang, Q, Gumireddy, K, Schrier, M et al. (2008) The microRNAs miR-373 and miR-520c promote tumor invasion and metastasis. Nat Cell Biol. 10: 202–210.CrossRefGoogle Scholar
Tavazoie, SF, Alarcón, C, Oskarsson, T et al. (2008) Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 451: 147–152.CrossRefGoogle ScholarPubMed
Lujambio, A, Esteller, M (2007) CpG island hypermethylation of tumor suppressor microRNAs in human cancer. Cell Cycle. 6: 1455–1459.CrossRefGoogle ScholarPubMed
Saito, Y, Liang, G, Egger, G et al. (2006) Specific activation of microRNA-127 with downregulation of the protooncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 9: 435–443.CrossRefGoogle Scholar
Lujambio, A, Ropero, S, Ballestar, E et al. (2007) Genetic unmasking of an epigenetically silenced microRNA in human cancer cells. Cancer Res. 67: 1424–1429.CrossRefGoogle ScholarPubMed
Lehmann, U, Hasemeier, B, Christgen, M et al. (2008) Epigenetic inactivation of microRNA gene hsa-mir-9–1 in human breast cancer. J Pathol. 214: 17–24.CrossRefGoogle ScholarPubMed
Kozaki, K, Imoto, I, Mogi, S, Omura, K, Inazawa, J (2008) Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in oral cancer. Cancer Res. 68: 2094–2105.CrossRefGoogle ScholarPubMed
Grady, WM, Parkin, RK, Mitchell, PS et al. (2008) Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer. Oncogene. 27: 3880–3888.CrossRefGoogle ScholarPubMed
Yoo, CB, Jones, PA (2006) Epigenetic therapy of cancer: Past, present and future. Nat Rev Drug Discov. 5: 37–50.CrossRefGoogle ScholarPubMed
Lujambio, A, Calin, GA, Villanueva, A et al. (2008) A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci USA. (in press) 105: 13556–13561.CrossRefGoogle ScholarPubMed
Villar-Garea, A, Esteller, M (2004) Histone deacetylase inhibitors: understanding a new wave of anticancer agents. Int J Cancer. 112: 171–178.CrossRefGoogle ScholarPubMed
Sadikovic, B, Andrews, J, Carter, D, Robinson, J, Rodenhiser, DI (2008) Genome-wide H3K9 histone acetylation profiles are altered in benzopyrene-treated MCF7 breast cancer cells. J Biol Chem. 283: 4051–4060.CrossRefGoogle ScholarPubMed
Shukeir, N, Pakneshan, P, Chen, G, Szyf, M, Rabbani, SA (2006) Alteration of the methylation status of tumor-promoting genes decreases prostate cancer cell invasiveness and tumorigenesis in vitro and in vivo. Cancer Res. 66: 9202–9210.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×