Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1096K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bachelder, R. E. Articles by Mercurio, A. M. Search for Related Content PubMed PubMed Citation Articles by Bachelder, R. E. Articles by Mercurio, A. M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Genetics Home Reference Social Bookmarking                      What's this?

Robin E. Bachelder¹, Sang-Oh Yoon¹, Clara Franci², Antonio García de Herreros², and Arthur M. Mercurio¹

¹ Department of Pathology, Division of Cancer Biology and Angiogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215
² Unitat de Biologia Cellular i Molecular, Institut Municipal d'Investigació Mèdica, Universitat Pompeu Fabra, 08003 Barcelona, Spain

Correspondence to Robin E. Bachelder: rbacheld{at}bidmc.harvard.edu

Abstract
We report that the activity of glycogen synthase kinase-3 (GSK-3) is necessary for the maintenance of the epithelial architecture. Pharmacological inhibition of its activity or reducing its expression using small interfering RNAs in normal breast and skin epithelial cells results in a reduction of E-cadherin expression and a more mesenchymal morphology, both of which are features associated with an epithelial–mesenchymal transition (EMT). Importantly, GSK-3 inhibition also stimulates the transcription of Snail, a repressor of E-cadherin and an inducer of the EMT. We identify NFB as a transcription factor inhibited by GSK-3 in epithelial cells that is relevant for Snail expression. These findings indicate that epithelial cells must sustain activation of a specific kinase to impede a mesenchymal transition.

Abbreviations used in this paper: EMT, epithelial–mesenchymal transition; GSK-3, glycogen synthase kinase-3; siRNA, small interfering RNA.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Strippoli, R., Benedicto, I., Perez Lozano, M. L., Cerezo, A., Lopez-Cabrera, M., del Pozo, M. A. (2008). Epithelial-to-mesenchymal transition of peritoneal mesothelial cells is regulated by an ERK/NF-{kappa}B/Snail1 pathway. DMM 1: 264-274 [Abstract] [Full Text]  
• Lee, M.-Y., Chou, C.-Y., Tang, M.-J., Shen, M.-R. (2008). Epithelial-Mesenchymal Transition in Cervical Cancer: Correlation with Tumor Progression, Epidermal Growth Factor Receptor Overexpression, and Snail Up-Regulation. Clin. Cancer Res. 14: 4743-4750 [Abstract] [Full Text]  
• Assi, K, Mills, J, Owen, D, Ong, C, St Arnaud, R, Dedhar, S, Salh, B (2008). Integrin-linked kinase regulates cell proliferation and tumour growth in murine colitis-associated carcinogenesis. Gut 57: 931-940 [Abstract] [Full Text]  
• Kattla, J. J., Carew, R. M., Heljic, M., Godson, C., Brazil, D. P. (2008). Protein kinase B/Akt activity is involved in renal TGF-{beta}1-driven epithelial-mesenchymal transition in vitro and in vivo. Am. J. Physiol. Renal Physiol. 295: F215-F225 [Abstract] [Full Text]  
• Kong, D., Wang, Z., Sarkar, S. H., Li, Y., Banerjee, S., Saliganan, A., Kim, H.-R. C., Cher, M. L., Sarkar, F. H. (2008). Platelet-Derived Growth Factor-D Overexpression Contributes to Epithelial-Mesenchymal Transition of PC3 Prostate Cancer Cells. Stem Cells 26: 1425-1435 [Abstract] [Full Text]  
• Huang, W., Zhang, Y., Varambally, S., Chinnaiyan, A. M., Banerjee, M., Merajver, S. D., Kleer, C. G. (2008). Inhibition of CCN6 (Wnt-1-Induced Signaling Protein 3) Down-Regulates E-Cadherin in the Breast Epithelium through Induction of Snail and ZEB1. Am. J. Pathol. 172: 893-904 [Abstract] [Full Text]  
• Ullmann, U., Gilles, C., De Rycke, M., Van de Velde, H., Sermon, K., Liebaers, I. (2008). GSK-3-specific inhibitor-supplemented hESC medium prevents the epithelial-mesenchymal transition process and the up-regulation of matrix metalloproteinases in hESCs cultured in feeder-free conditions. Mol Hum Reprod 14: 169-179 [Abstract] [Full Text]  
• Song, Y., Zhao, C., Dong, L., Fu, M., Xue, L., Huang, Z., Tong, T., Zhou, Z., Chen, A., Yang, Z., Lu, N., Zhan, Q. (2008). Overexpression of cyclin B1 in human esophageal squamous cell carcinoma cells induces tumor cell invasive growth and metastasis. Carcinogenesis 29: 307-315 [Abstract] [Full Text]  
• Criswell, T. L., Arteaga, C. L. (2007). Modulation of NF{kappa}B Activity and E-cadherin by the Type III Transforming Growth Factor beta Receptor Regulates Cell Growth and Motility. J. Biol. Chem. 282: 32491-32500 [Abstract] [Full Text]  
• El Touny, L. H., Banerjee, P. P. (2007). Akt GSK-3 pathway as a target in genistein-induced inhibition of TRAMP prostate cancer progression toward a poorly differentiated phenotype. Carcinogenesis 28: 1710-1717 [Abstract] [Full Text]  
• Lester, R. D., Jo, M., Montel, V., Takimoto, S., Gonias, S. L. (2007). uPAR induces epithelial mesenchymal transition in hypoxic breast cancer cells. JCB 178: 425-436 [Abstract] [Full Text]  
• Palmer, M. B., Majumder, P., Green, M. R., Wade, P. A., Boss, J. M. (2007). A 3' Enhancer Controls Snail Expression in Melanoma Cells. Cancer Res. 67: 6113-6120 [Abstract] [Full Text]  
• Belguise, K., Guo, S., Sonenshein, G. E. (2007). Activation of FOXO3a by the Green Tea Polyphenol Epigallocatechin-3-Gallate Induces Estrogen Receptor {alpha} Expression Reversing Invasive Phenotype of Breast Cancer Cells. Cancer Res. 67: 5763-5770 [Abstract] [Full Text]  
• Kim, H.-J., Litzenburger, B. C., Cui, X., Delgado, D. A., Grabiner, B. C., Lin, X., Lewis, M. T., Gottardis, M. M., Wong, T. W., Attar, R. M., Carboni, J. M., Lee, A. V. (2007). Constitutively Active Type I Insulin-Like Growth Factor Receptor Causes Transformation and Xenograft Growth of Immortalized Mammary Epithelial Cells and Is Accompanied by an Epithelial-to-Mesenchymal Transition Mediated by NF-{kappa}B and Snail. Mol. Cell. Biol. 27: 3165-3175 [Abstract] [Full Text]  
• Larriba, M. J., Valle, N., Palmer, H. G, Ordonez-Moran, P., Alvarez-Diaz, S., Becker, K.-F., Gamallo, C., de Herreros, A. G., Gonzalez-Sancho, J. M., Munoz, A. (2007). The inhibition of Wnt/{beta}-catenin signalling by 1{alpha},25-dihydroxyvitamin D3 is abrogated by Snail1 in human colon cancer cells. Endocr Relat Cancer 14: 141-151 [Abstract] [Full Text]  
• Martinez, M. J., Smith, A. D., Li, B., Zhang, M. Q., Harrod, K. S. (2007). Computational prediction of novel components of lung transcriptional networks. Bioinformatics 23: 21-29 [Abstract] [Full Text]  
• Lim, H.-Y., Tomlinson, A. (2006). Organization of the peripheral fly eye: the roles of Snail family transcription factors in peripheral retinal apoptosis. Development 133: 3529-3537 [Abstract] [Full Text]  
• Dasari, V., Gallup, M., Lemjabbar, H., Maltseva, I., McNamara, N. (2006). Epithelial-Mesenchymal Transition in Lung Cancer: Is Tobacco the "Smoking Gun"?. Am. J. Respir. Cell Mol. Bio. 35: 3-9 [Full Text]  
• Rukstalis, J. M., Ubeda, M., Johnson, M. V., Habener, J. F. (2006). Transcription Factor Snail Modulates Hormone Expression in Established Endocrine Pancreatic Cell Lines. Endocrinology 147: 2997-3006 [Abstract] [Full Text]  
• Medici, D., Hay, E. D., Goodenough, D. A. (2006). Cooperation between Snail and LEF-1 Transcription Factors Is Essential for TGF-beta1-induced Epithelial-Mesenchymal Transition. Mol. Biol. Cell 17: 1871-1879 [Abstract] [Full Text]  
• Shin, S. R., Sanchez-Velar, N., Sherr, D. H., Sonenshein, G. E. (2006). 7,12-Dimethylbenz(a)Anthracene Treatment of a c-rel Mouse Mammary Tumor Cell Line Induces Epithelial to Mesenchymal Transition via Activation of Nuclear Factor-{kappa}B.. Cancer Res. 66: 2570-2575 [Abstract] [Full Text]  
• Izzo, J. G., Malhotra, U., Wu, T.-T., Ensor, J., Luthra, R., Lee, J. H., Swisher, S. G., Liao, Z., Chao, K.S. C., Hittelman, W. N., Aggarwal, B. B., Ajani, J. A. (2006). Association of Activated Transcription Factor Nuclear Factor {kappa}B With Chemoradiation Resistance and Poor Outcome in Esophageal Carcinoma. JCO 24: 748-754 [Abstract] [Full Text]  
• Peiro, S., Escriva, M., Puig, I., Barbera, M. J., Dave, N., Herranz, N., Larriba, M. J., Takkunen, M., Franci, C., Munoz, A., Virtanen, I., Baulida, J., de Herreros, A. G. (2006). Snail1 transcriptional repressor binds to its own promoter and controls its expression.. Nucleic Acids Res 34: 2077-2084 [Abstract] [Full Text]  
• Plante, I., Cyr, D. G., Charbonneau, M. (2005). Involvement of the Integrin-Linked Kinase Pathway in Hexachlorobenzene-Induced Gender-Specific Rat Hepatocarcinogenesis. Toxicol Sci 88: 346-357 [Abstract] [Full Text]  
• Steinbrecher, K. A., Wilson, W. III, Cogswell, P. C., Baldwin, A. S. (2005). Glycogen Synthase Kinase 3{beta} Functions To Specify Gene-Specific, NF-{kappa}B-Dependent Transcription. Mol. Cell. Biol. 25: 8444-8455 [Abstract] [Full Text]  
• Carrozzino, F., Soulie, P., Huber, D., Mensi, N., Orci, L., Cano, A., Feraille, E., Montesano, R. (2005). Inducible expression of Snail selectively increases paracellular ion permeability and differentially modulates tight junction proteins. Am. J. Physiol. Cell Physiol. 289: C1002-C1014 [Abstract] [Full Text]  
• Barrallo-Gimeno, A., Nieto, M. A. (2005). The Snail genes as inducers of cell movement and survival: implications in development and cancer. Development 132: 3151-3161 [Abstract] [Full Text]  
• Yoon, S.-O., Shin, S., Mercurio, A. M. (2005). Hypoxia Stimulates Carcinoma Invasion by Stabilizing Microtubules and Promoting the Rab11 Trafficking of the {alpha}6{beta}4 Integrin. Cancer Res. 65: 2761-2769 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents