This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lagana, A. Articles by Nabi, I. R. Search for Related Content PubMed PubMed Citation Articles by Lagana, A. Articles by Nabi, I. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2006, p. 3181-3193, Vol. 26, No. 8
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.8.3181-3193.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Galectin Binding to Mgat5-Modified N-Glycans Regulates Fibronectin Matrix Remodeling in Tumor Cells

Annick Lagana,^1, Jacky G. Goetz,^1,2, Pam Cheung,³ Avraham Raz,⁴ James W. Dennis,³ and Ivan R. Nabi^1,2*

Department of Pathology and Cell Biology, Université de Montréal, Québec, Canada,¹ Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, BC, Canada,² Samuel Lunenfeld Research Institute, Toronto, Ontario, Canada,³ Karmanos Cancer Institute, Detroit, Michigan⁴

Received 22 September 2005/ Returned for modification 1 November 2005/ Accepted 21 January 2006

Oncogenic signaling stimulates the dynamic remodeling of actin microfilaments and substrate adhesions, essential for cell spreading and motility. Transformation is associated with increased expression of ß1,6GlcNAc-branched N-glycans, products of Golgi ß1,6-acetylglucosaminyltransferase V (Mgat5) and the favored ligand for galectins. Herein we report that fibronectin fibrillogenesis and fibronectin-dependent cell spreading are deficient in Mgat5^–/– mammary epithelial tumor cells and inhibited in Mgat5^+/+ cells by blocking Golgi N-glycan processing with swainsonine or by competitive inhibition of galectin binding. At an optimum dosage, exogenous galectin-3 added to Mgat5^+/+ cells activates focal adhesion kinase (FAK) and phosphatidylinositol 3-kinase (PI3K), recruits conformationally active 5ß1-integrin to fibrillar adhesions, and increases F-actin turnover. RGD peptide inhibits PI3K-dependent fibronectin matrix remodeling and fibronectin-dependent cell motility, while galectin-3 stimulates and overrides the inhibitory effects of RGD. Antibodies to the galectin-3 N-terminal oligomerization domain stimulate 5ß1 activation and recruitment to fibrillar adhesions in Mgat5^+/+ cells, an effect that is blocked by disrupting galectin-glycan binding. Our results demonstrate that fibronectin polymerization and tumor cell motility are regulated by galectin-3 binding to branched N-glycan ligands that stimulate focal adhesion remodeling, FAK and PI3K activation, local F-actin instability, and 5ß1 translocation to fibrillar adhesions.

These authors contributed equally.

This article has been cited by other articles:

• Karmakar, S., Stowell, S. R, Cummings, R. D, McEver, R. P (2008). Galectin-1 signaling in leukocytes requires expression of complex-type N-glycans. Glycobiology 18: 770-778 [Abstract] [Full Text]  
• Lau, K. S, Dennis, J. W (2008). N-Glycans in cancer progression. Glycobiology 18: 750-760 [Abstract] [Full Text]  
• Zavareh, R. B., Lau, K. S., Hurren, R., Datti, A., Ashline, D. J., Gronda, M., Cheung, P., Simpson, C. D., Liu, W., Wasylishen, A. R., Boutros, P. C., Shi, H., Vengopal, A., Jurisica, I., Penn, L. Z., Reinhold, V. N., Ezzat, S., Wrana, J., Rose, D. R., Schachter, H., Dennis, J. W., Schimmer, A. D. (2008). Inhibition of the Sodium/Potassium ATPase Impairs N-Glycan Expression and Function. Cancer Res. 68: 6688-6697 [Abstract] [Full Text]  
• Hedlund, M., Ng, E., Varki, A., Varki, N. M. (2008). {alpha}2-6 Linked Sialic Acids on N-Glycans Modulate Carcinoma Differentiation In vivo. Cancer Res. 68: 388-394 [Abstract] [Full Text]  
• Lajoie, P., Partridge, E. A., Guay, G., Goetz, J. G., Pawling, J., Lagana, A., Joshi, B., Dennis, J. W., Nabi, I. R. (2007). Plasma membrane domain organization regulates EGFR signaling in tumor cells. J. Cell Biol. 179: 341-356 [Abstract] [Full Text]  
• Friedrichs, J., Torkko, J. M., Helenius, J., Teravainen, T. P., Fullekrug, J., Muller, D. J., Simons, K., Manninen, A. (2007). Contributions of Galectin-3 and -9 to Epithelial Cell Adhesion Analyzed by Single Cell Force Spectroscopy. J. Biol. Chem. 282: 29375-29383 [Abstract] [Full Text]  
• de Melo, F. H.M., Butera, D., Medeiros, R. S., Andrade, L. N. d. S., Nonogaki, S., Soares, F. A., Alvarez, R. A., Moura da Silva, A. M., Chammas, R. (2007). Biological Applications of a Chimeric Probe for the Assessment of Galectin-3 Ligands. J. Histochem. Cytochem. 55: 1015-1026 [Abstract] [Full Text]  
• Cheung, P., Dennis, J. W. (2007). Mgat5 and Pten interact to regulate cell growth and polarity. Glycobiology 17: 767-773 [Abstract] [Full Text]