V600EBRAF promotes invasiveness of thyroid cancer cells by decreasing E-cadherin expression through a Snail-dependent mechanism

被引：60

作者：

Baquero, Pablo ^{[1
]}

Sanchez-Hernandez, Irene ^{[1
]}

Jimenez-Mora, Eva ^{[1
]}

Orgaz, Jose L. ^{[2
]}

Jimenez, Benilde ^{[2
]}

Chiloeches, Antonio ^{[1
]}

机构：

[1] Univ Alcala de Henares, Fac Med, Dept Bioquim & Biol Mol, E-28871 Madrid, Spain

[2] Univ Autonoma Madrid, Madrid Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols, Dept Bioquim, Madrid, Spain

来源：

CANCER LETTERS | 2013年 / 335卷 / 01期

关键词：

BRAF; Snail; E-cadherin; EMT; Invasion; Thyroid cancer; EPITHELIAL-MESENCHYMAL TRANSITION; GENE-EXPRESSION; BRAF MUTATION; B-RAF; CARCINOMA; KINASE; BRAF(V600E); PROGRESSION; INHIBITORS; METHYLATION;

D O I：

10.1016/j.canlet.2013.02.033

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

BRAF is a main oncogene in human thyroid cancer. Here, we show that BRAF depletion by siRNA or inhibition of its activity by treatment with BRAF inhibitor PLX4720 decreases migration and invasion in thyroid cancer cells expressing oncogenic (V600E)BRAF through a MEK/ERK-dependent mechanism, since treatment with the MEK inhibitor U0126 exerts the same effect. Moreover, over-expression of (V600E)BRAF increases migration and invasion of wild-type BRAF thyroid cells. Using the same strategies, we demonstrate that these effects are mediated by upregulation of the transcriptional repressor Snail with a concomitant decrease of its target E-cadherin, both hallmarks of EMT. These results reveal a novel (V600E)BRAF-induced mechanism in thyroid tumours progression and provides a rationale for using the PLX4720 inhibitor to target (V600E)BRAF signalling to effectively control progression of thyroid cancer. (c) 2013 Elsevier Ireland Ltd. All rights reserved.

引用

页码：232 / 241

页数：10

共 50 条

[11] Epithelial-mesenchymal transition and tumour invasion [J].

Guarino, Marcello .

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2007, 39 (12) :2153-2160

[12] Snail family transcription factors are implicated in thyroid carcinogenesis [J].

Hardy, Robert G. ;

Vicente-Duenas, Carolina ;

Gonzalez-Herrero, Ines ;

Anderson, Catriona ;

Flores, Teresa ;

Hughes, Sharon ;

Tselepis, Chris ;

Ross, James A. ;

Sanchez-Garcia, Isidro .

AMERICAN JOURNAL OF PATHOLOGY, 2007, 171 (03) :1037-1046

[13] RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth [J].

Hatzivassiliou, Georgia ;

Song, Kyung ;

Yen, Ivana ;

Brandhuber, Barbara J. ;

Anderson, Daniel J. ;

Alvarado, Ryan ;

Ludlam, Mary J. C. ;

Stokoe, David ;

Gloor, Susan L. ;

Vigers, Guy ;

Morales, Tony ;

Aliagas, Ignacio ;

Liu, Bonnie ;

Sideris, Steve ;

Hoeflich, Klaus P. ;

Jaiswal, Bijay S. ;

Seshagiri, Somasekar ;

Koeppen, Hartmut ;

Belvin, Marcia ;

Friedman, Lori S. ;

Malek, Shiva .

NATURE, 2010, 464 (7287) :431-U132

[14] Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer [J].

Hu, Shuiying ;

Liu, Dingxie ;

Tufano, Ralph P. ;

Carson, Kathryn A. ;

Rosenbaum, Eli ;

Cohen, Yoram ;

Holt, Elizabeth H. ;

Kiseljak-Vassiliades, Katja ;

Rhoden, Kerry J. ;

Tolaney, Sara ;

Condouris, Stephen ;

Tallini, Giovanni ;

Westra, William H. ;

Umbricht, Christopher B. ;

Zeiger, Martha A. ;

Califano, Joseph A. ;

Vasko, Vasily ;

Xing, Mingzhao .

INTERNATIONAL JOURNAL OF CANCER, 2006, 119 (10) :2322-2329

[15] Molecular requirements for epithelial-mesenchymal transition during tumor progression [J].

Huber, MA ;

Kraut, N ;

Beug, H .

CURRENT OPINION IN CELL BIOLOGY, 2005, 17 (05) :548-558

[16] B-RAF is a therapeutic target in melanoma [J].

Karasarides, M ;

Chiloeches, A ;

Hayward, R ;

Niculescu-Duvaz, D ;

Scanlon, I ;

Friedlos, F ;

Ogilvie, L ;

Hedley, D ;

Martin, J ;

Marshall, CJ ;

Springer, CJ ;

Marais, R .

ONCOGENE, 2004, 23 (37) :6292-6298

[17] Aggressive Variants of Papillary Thyroid Cancer: Incidence, Characteristics and Predictors of Survival among 43,738 Patients [J].

Kazaure, Hadiza S. ;

Roman, Sanziana A. ;

Sosa, Julie A. .

ANNALS OF SURGICAL ONCOLOGY, 2012, 19 (06) :1874-1880

[18] Progression of BRAF-induced thyroid cancer is associated with epithelial-mesenchymal transition requiring concomitant MAP kinase and TGFβ signaling [J].

Knauf, J. A. ;

Sartor, M. A. ;

Medvedovic, M. ;

Lundsmith, E. ;

Ryder, M. ;

Salzano, M. ;

Nikiforov, Y. E. ;

Giordano, T. J. ;

Ghossein, R. A. ;

Fagin, J. A. .

ONCOGENE, 2011, 30 (28) :3153-3162

[19] Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation [J].

Knauf, JA ;

Ma, XL ;

Smith, EP ;

Zhang, L ;

Mitsutake, N ;

Liao, XH ;

Refetoff, S ;

Nikiforov, YE ;

Fagin, JA .

CANCER RESEARCH, 2005, 65 (10) :4238-4245

[20]

Lin Kimberly, 2010, Genes Cancer, V1, P409

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