A Comprehensive DNA Methylation Profile of Epithelial-to-Mesenchymal Transition

被引：65

作者：

Carmona, F. Javier ^{[1
]}

Davalos, Veronica ^{[1
]}

Vidal, Enrique ^{[1
]}

Gomez, Antonio ^{[1
]}

Heyn, Holger ^{[1
]}

Hashimoto, Yutaka ^{[1
]}

Vizoso, Miguel ^{[1
]}

Martinez-Cardus, Anna ^{[1
]}

Sayols, Sergi ^{[1
]}

Ferreira, Humberto J. ^{[1
]}

Sanchez-Mut, Jose V. ^{[1
]}

Moran, Sebastian ^{[1
]}

Margel, Mireia ^{[2
]}

Castella, Eva ^{[3
]}

Berdasco, Maria ^{[1
]}

Stefansson, Olafur A. ^{[1
]}

Eyfjord, Jorunn E. ^{[4
,5
]}

Gonzalez-Suarez, Eva ^{[1
]}

Dopazo, Joaquin ^{[6
,7
,8
]}

Orozco, Modesto ^{[9
,10
,11
,12
]}

Gut, Ivo G. ^{[13
]}

Esteller, Manel ^{[1
,14
,15
]}

机构：

[1] Hosp Llobregat, Canc Epigenet & Biol Program PEBC, Bellvitge Biomed Res Inst, Barcelona 08908, Spain

[2] Catalan Inst Oncol Badalona, Barcelona, Spain

[3] Hosp Badalona Germans Trias & Pujol, Dept Pathol, Badalona, Spain

[4] Univ Iceland, Fac Med, Canc Res Lab, Reykjavik, Iceland

[5] Univ Iceland, Dept Med, Reykjavik, Iceland

[6] CIPF, Dept Bioinformat, Valencia, Spain

[7] CIBER Enfermedades Raras CIBERER, Valencia, Spain

[8] CIPF, Funct Genom Node INB, Valencia, Spain

[9] IRB Barcelona, Inst Res Biomed, Barcelona, Spain

[10] Joint IRB BSC Res Program Computat Biol, Barcelona, Spain

[11] Barcelona Supercomputing Ctr, Barcelona, Spain

[12] Univ Barcelona, Dept Biochem & Mol Biol, Barcelona, Spain

[13] CNAG, Barcelona, Spain

[14] Univ Barcelona, Sch Med, Dept Physiol Sci 2, Barcelona, Spain

[15] ICREA, Barcelona, Spain

来源：

CANCER RESEARCH | 2014年 / 74卷 / 19期

基金：

欧洲研究理事会;

关键词：

INTEGRIN ALPHA(5); CANCER; METASTASIS; EXPRESSION; SUPPRESSION; MICROARRAY; CARCINOMA; PROTEINS; FKBP65; MODEL;

D O I：

10.1158/0008-5472.CAN-13-3659

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Epithelial-to-mesenchymal transition (EMT) is a plastic process in which fully differentiated epithelial cells are converted into poorly differentiated, migratory and invasive mesenchymal cells, and it has been related to the metastasis potential of tumors. This is a reversible process and cells can also eventually undergo mesenchymal-to-epithelial transition. The existence of a dynamic EMT process suggests the involvement of epigenetic shifts in the phenotype. Herein, we obtained the DNA methylomes at single-base resolution of Madin-Darby canine kidney cells undergoing EMT and translated the identified differentially methylated regions to human breast cancer cells undergoing a gain of migratory and invasive capabilities associated with the EMT phenotype. We noticed dynamic and reversible changes of DNA methylation, both on promoter sequences and gene-bodies in association with transcription regulation of EMT-related genes. Most importantly, the identified DNA methylation markers of EMT were present in primary mammary tumors in association with the epithelial or the mesenchymal phenotype of the studied breast cancer samples. (C) 2014 AACR.

引用

页码：5608 / 5619

页数：12

共 52 条

[1]

Multi-Platform Whole-Genome Microarray Analyses Refine the Epigenetic Signature of Breast Cancer Metastasis with Gene Expression and Copy Number [J].

Andrews, Joseph ;

Kennette, Wendy ;

Pilon, Jenna ;

Hodgson, Alexandra ;

Tuck, Alan B. ;

Chambers, Ann F. ;

Rodenhiser, David I. .

PLOS ONE, 2010, 5 (01)

[2]

Targeted and genome-scale strategies reveal gene-body methylation signatures in human cells [J].

Ball, Madeleine P. ;

Li, Jin Billy ;

Gao, Yuan ;

Lee, Je-Hyuk ;

LeProust, Emily M. ;

Park, In-Hyun ;

Xie, Bin ;

Daley, George Q. ;

Church, George M. .

NATURE BIOTECHNOLOGY, 2009, 27 (04) :361-368

[3]

A decade of exploring the cancer epigenome - biological and translational implications [J].

Baylin, Stephen B. ;

Jones, Peter A. .

NATURE REVIEWS CANCER, 2011, 11 (10) :726-734

[4]

Berdasco Maria, 2009, V507, P23, DOI 10.1007/978-1-59745-522-0_2

[5]

The NIH Roadmap Epigenomics Mapping Consortium [J].

Bernstein, Bradley E. ;

Stamatoyannopoulos, John A. ;

Costello, Joseph F. ;

Ren, Bing ;

Milosavljevic, Aleksandar ;

Meissner, Alexander ;

Kellis, Manolis ;

Marra, Marco A. ;

Beaudet, Arthur L. ;

Ecker, Joseph R. ;

Farnham, Peggy J. ;

Hirst, Martin ;

Lander, Eric S. ;

Mikkelsen, Tarjei S. ;

Thomson, James A. .

NATURE BIOTECHNOLOGY, 2010, 28 (10) :1045-1048

[6]

High density DNA methylation array with single CpG site resolution [J].

Bibikova, Marina ;

Barnes, Bret ;

Tsan, Chan ;

Ho, Vincent ;

Klotzle, Brandy ;

Le, Jennie M. ;

Delano, David ;

Zhang, Lu ;

Schroth, Gary P. ;

Gunderson, Kevin L. ;

Fan, Jian-Bing ;

Shen, Richard .

GENOMICS, 2011, 98 (04) :288-295

[7]

To differentiate or not - routes towards metastasis [J].

Brabletz, Thomas .

NATURE REVIEWS CANCER, 2012, 12 (06) :425-436

[8]

Suppression of the Epithelial-Mesenchymal Transition by Grainyhead-like-2 [J].

Cieply, Benjamin ;

Riley, Philip ;

Pifer, Phillip M. ;

Widmeyer, Joseph ;

Addison, Joseph B. ;

Ivanov, Alexey V. ;

Denvir, James ;

Frisch, Steven M. .

CANCER RESEARCH, 2012, 72 (09) :2440-2453

[9]

Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis [J].

Davalos, V. ;

Moutinho, C. ;

Villanueva, A. ;

Boque, R. ;

Silva, P. ;

Carneiro, F. ;

Esteller, M. .

ONCOGENE, 2012, 31 (16) :2062-2074

[10]

Annual Report to the Nation on the Status of Cancer, 1975-2006, Featuring Colorectal Cancer Trends and Impact of Interventions (Risk Factors, Screening, and Treatment) to Reduce Future Rates [J].

Edwards, Brenda K. ;

Ward, Elizabeth ;

Kohler, Betsy A. ;

Eheman, Christie ;

Zauber, Ann G. ;

Anderson, Robert N. ;

Jemal, Ahmedin ;

Schymura, Maria J. ;

Lansdorp-Vogelaar, Iris ;

Seeff, Laura C. ;

van Ballegooijen, Marjolein ;

Goede, S. Luuk ;

Ries, Lynn A. G. .

CANCER, 2010, 116 (03) :544-573

← 1 2 3 4 5 6 →