hnRNP A2/B1 Modulates Epithelial-Mesenchymal Transition in Lung Cancer Cell Lines

被引：98

作者：

Tauler, Jordi ^{[1
]}

Zudaire, Enrique ^{[2
]}

Liu, Huaitian ^{[3
]}

Shih, Joanna ^{[4
]}

Mulshine, James L. ^{[1
]}

机构：

[1] Rush Univ, Med Ctr, Sect Med Oncol, Lab Lung Canc Biol, Chicago, IL 60612 USA

[2] NCI, Angiogenesis Core Facil, NIH, Adv Technol Ctr, Gaithersburg, MD USA

[3] Sci Applicat Int Corp, Rockville, MD USA

[4] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA

来源：

CANCER RESEARCH | 2010年 / 70卷 / 18期

关键词：

NUCLEAR RIBONUCLEOPROTEIN A2/B1; DETECTION MARKER; EXPRESSION; PROTEIN; A2; ANTIGEN; RNA; P53; OVEREXPRESSION; IDENTIFICATION;

D O I：

10.1158/0008-5472.CAN-10-0860

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) has been reported to be overexpressed in lung cancer and in other cancers such as breast, pancreas, and liver. However, a mechanism linking hnRNP A2/B1 overexpression and progression to cancer has not yet been definitively established. To elucidate this mechanism, we have silenced hnRNPA2/B1 mRNA in non-small-cell lung cancer cell lines A549, H1703, and H358. These cell lines present different levels of expression of epithelial-to-mesenchymal transition (EMT) markers such as E-cadherin, fibronectin, and vimentin. Microarray expression analysis was performed to evaluate the effect of silencing hnRNP A2/B1 in A549 cells. We identified a list of target genes, affected by silencing of hnRNP A2/B1, that are involved in regulation of migration, proliferation, survival, and apoptosis. Silencing hnRNP A2/B1 induced formation of cell clusters and increased proliferation. In the anchorage-independent assay, silencing hnRNP A2/B1 increased colony formation by 794% in A549 and 174% in H1703 compared with a 25% increase in proliferation, in both cell lines, in a two-dimensional proliferation assay. Silencing hnRNP A2/B1 decreased migration in intermediate cell line A549 and mesenchymal cell line H1703; however, no changes in proliferation were observed in epithelial cell line H358. Silencing hnRNP A2/B1 in A549 and H1703 cells correlated with an increase of E-cadherin expression and downregulation of the E-cadherin inhibitors Twist1 and Snai1. These data suggest that expression of hnRNP A2/B1 may play a role in EMT, in nonepithelial lung cancer cell lines A549 and H1703, through the regulation of E-cadherin expression. Cancer Res; 70(18); 7137-47. (C)2010 AACR.

引用

页码：7137 / 7147

页数：11

共 43 条

[1] Role of macrophage inhibitory cytokine-1 in tumorigenesis and diagnosis of cancer [J].

Bauskin, Asne R. ;

Brown, David A. ;

Kuffner, Tamara ;

Johnen, Heiko ;

Luo, X. Wei ;

Hunter, Mark ;

Breit, Samuel N. .

CANCER RESEARCH, 2006, 66 (10) :4983-4986

[2] The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism [J].

Clower, Cynthia V. ;

Chatterjee, Deblina ;

Wang, Zhenxun ;

Cantley, Lewis C. ;

Heiden, Matthew G. Vander ;

Krainer, Adrian R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (05) :1894-1899

[3] RNA and Disease [J].

Cooper, Thomas A. ;

Wan, Lili ;

Dreyfuss, Gideon .

CELL, 2009, 136 (04) :777-793

[4] Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis [J].

D'Orazi, G ;

Cecchinelli, B ;

Bruno, T ;

Manni, I ;

Higashimoto, Y ;

Saito, S ;

Gostissa, M ;

Coen, S ;

Marchetti, A ;

Del Sal, G ;

Piaggio, G ;

Fanciulli, M ;

Appella, E ;

Soddu, S .

NATURE CELL BIOLOGY, 2002, 4 (01) :11-19

[5] HIPK2 neutralizes MDM2 inhibition rescuing p53 transcriptional activity and apoptotic function [J].

Di Stefano, V ;

Blandino, G ;

Sacchi, A ;

Soddu, S ;

D'Orazi, G .

ONCOGENE, 2004, 23 (30) :5185-5192

[6] Messenger-RNA-binding proteins and the messages they carry [J].

Dreyfuss, G ;

Kim, VN ;

Kataoka, N .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2002, 3 (03) :195-205

[7]

Fielding P, 1999, CLIN CANCER RES, V5, P4048

[8] Heterogeneous Nuclear Ribonucleoprotein A2 Is a Common Transcriptional Coactivator in the Nuclear Transcription Response to Mitochondrial Respiratory Stress [J].

Guha, Manti ;

Pan, Hua ;

Fang, Ji-Kang ;

Avadhani, Narayan G. .

MOLECULAR BIOLOGY OF THE CELL, 2009, 20 (18) :4107-4119

[9] The hallmarks of cancer [J].

Hanahan, D ;

Weinberg, RA .

CELL, 2000, 100 (01) :57-70

[10] Downstream Targets of Heterogeneous Nuclear Ribonucleoprotein A2 Mediate Cell Proliferation [J].

He, Yaowu ;

Rothnagel, Joseph A. ;

Epis, Michael R. ;

Leedman, Peter J. ;

Smith, Ross .

MOLECULAR CARCINOGENESIS, 2009, 48 (02) :167-179

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