This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gong, H. C. Articles by Raz, A. Search for Related Content PubMed PubMed Citation Articles by Gong, H. C. Articles by Raz, A.

The NH₂ Terminus of Galectin-3 Governs Cellular Compartmentalization and Functions in Cancer Cells¹

Metastasis Research Program, Karmanos Cancer Institute, Detroit, Michigan 48201 [H. C. G., Y. H., P. N-M., V. H., A. R.]; Department of Pathology, Radiation Oncology, Wayne State University, School of Medicine, Detroit, Michigan 48201 [A. R.]; Gastrointestinal Cancer Research Laboratory, Henry Ford Health Sciences Center, Detroit, Michigan 48202 [N. M., R. S. B.]

Galectin-3 is a member of the -galactoside-binding protein family shown to be involved in tumor progression and metastasis. It has a unique primary structure consisting of three domains: a 12-amino acid leader sequence containing a casein kinase I serine phosphorylation site, which is preceded by a collagenase-sensitive Pro-Gly-rich motif, and a COOH-terminal half encompassing the carbohydrate-binding site. To study the functional role of the unusual leader sequence of galectin-3, a mutant cDNA that causes an 11-amino acid deletion in the NH₂-terminal region was generated and expressed in galectin-3-null BT-549 human breast carcinoma cells. Deletion of the NH₂ terminus resulted in abolition of the secretion of truncated galectin-3, loss of nuclear localization, and reduced carbohydrate-mediated functions compared with the wild-type protein. When green fluorescent protein was fused to the galectin-3 leader sequence and transiently transfected into BT-549 cells, the uniform cellular distribution of native green fluorescent protein was changed mainly to a nuclear pattern. To further investigate whether the functional changes observed in a galectin-3 with the 11 NH₂-terminal amino acids deleted were due to loss of phosphorylation at Ser⁶, two point mutations were created at this serine: Ser⁶Ala and Ser⁶Glu. No obvious difference was observed in cellular localization between wild-type and Ser⁶-mutated transfectants. These results suggest a structural role for the NH₂ terminus leader motif of galectin-3 in determining its cellular targeting and biological functions independent of phosphorylation.

This article has been cited by other articles:

				Y. Wang, P. Nangia-Makker, L. Tait, V. Balan, V. Hogan, K. J. Pienta, and A. Raz Regulation of Prostate Cancer Progression by Galectin-3 Am. J. Pathol., April 1, 2009; 174(4): 1515 - 1523. [Abstract] [Full Text] [PDF]

				A. A. Mourad-Zeidan, V. O. Melnikova, H. Wang, A. Raz, and M. Bar-Eli Expression Profiling of Galectin-3-Depleted Melanoma Cells Reveals its Major Role in Melanoma Cell Plasticity and Vasculogenic Mimicry Am. J. Pathol., December 1, 2008; 173(6): 1839 - 1852. [Abstract] [Full Text] [PDF]

				R. Shalom-Feuerstein, S. J. Plowman, B. Rotblat, N. Ariotti, T. Tian, J. F. Hancock, and Y. Kloog K-Ras Nanoclustering Is Subverted by Overexpression of the Scaffold Protein Galectin-3 Cancer Res., August 15, 2008; 68(16): 6608 - 6616. [Abstract] [Full Text] [PDF]

				S. R. Kumar and S. L. Deutscher 111In-Labeled Galectin-3-Targeting Peptide as a SPECT Agent for Imaging Breast Tumors J. Nucl. Med., May 1, 2008; 49(5): 796 - 803. [Abstract] [Full Text] [PDF]

				J. G. Goetz, B. Joshi, P. Lajoie, S. S. Strugnell, T. Scudamore, L. D. Kojic, and I. R. Nabi Concerted regulation of focal adhesion dynamics by galectin-3 and tyrosine-phosphorylated caveolin-1 J. Cell Biol., March 24, 2008; 180(6): 1261 - 1275. [Abstract] [Full Text] [PDF]

				P. Nangia-Makker, T. Raz, L. Tait, V. Hogan, R. Fridman, and A. Raz Galectin-3 Cleavage: A Novel Surrogate Marker for Matrix Metalloproteinase Activity in Growing Breast Cancers Cancer Res., December 15, 2007; 67(24): 11760 - 11768. [Abstract] [Full Text] [PDF]

				F. H.M. de Melo, D. Butera, R. S. Medeiros, L. N. d. S. Andrade, S. Nonogaki, F. A. Soares, R. A. Alvarez, A. M. Moura da Silva, and R. Chammas Biological Applications of a Chimeric Probe for the Assessment of Galectin-3 Ligands J. Histochem. Cytochem., October 1, 2007; 55(10): 1015 - 1026. [Abstract] [Full Text] [PDF]

				F. L. Oliveira, P. Frazao, R. Chammas, D. K. Hsu, F. T. Liu, R. Borojevic, C. M. Takiya, and M. C. El-Cheikh Kinetics of mobilization and differentiation of lymphohematopoietic cells during experimental murine schistosomiasis in galectin-3 / mice J. Leukoc. Biol., August 1, 2007; 82(2): 300 - 310. [Abstract] [Full Text] [PDF]

				S. Nakahara, V. Hogan, H. Inohara, and A. Raz Importin-mediated Nuclear Translocation of Galectin-3 J. Biol. Chem., December 22, 2006; 281(51): 39649 - 39659. [Abstract] [Full Text] [PDF]

				S. Nakahara, N. Oka, Y. Wang, V. Hogan, H. Inohara, and A. Raz Characterization of the nuclear import pathways of galectin-3. Cancer Res., October 15, 2006; 66(20): 9995 - 10006. [Abstract] [Full Text] [PDF]

				P. J. Davidson, S.-Y. Li, A. G. Lohse, R. Vandergaast, E. Verde, A. Pearson, R. J. Patterson, J. L. Wang, and E. J. Arnoys Transport of galectin-3 between the nucleus and cytoplasm. I. Conditions and signals for nuclear import Glycobiology, July 1, 2006; 16(7): 602 - 611. [Abstract] [Full Text] [PDF]

				B. Cecchinelli, L. Lavra, C. Rinaldo, S. Iacovelli, A. Gurtner, A. Gasbarri, A. Ulivieri, F. Del Prete, M. Trovato, G. Piaggio, et al. Repression of the Antiapoptotic Molecule Galectin-3 by Homeodomain-Interacting Protein Kinase 2-Activated p53 Is Required for p53-Induced Apoptosis Mol. Cell. Biol., June 15, 2006; 26(12): 4746 - 4757. [Abstract] [Full Text] [PDF]

				A. Lagana, J. G. Goetz, P. Cheung, A. Raz, J. W. Dennis, and I. R. Nabi Galectin Binding to Mgat5-Modified N-Glycans Regulates Fibronectin Matrix Remodeling in Tumor Cells Mol. Cell. Biol., April 15, 2006; 26(8): 3181 - 3193. [Abstract] [Full Text] [PDF]

				N. Mazurek, Y. J. Sun, J. E. Price, L. Ramdas, W. Schober, P. Nangia-Makker, J. C. Byrd, A. Raz, and R. S. Bresalier Phosphorylation of Galectin-3 Contributes to Malignant Transformation of Human Epithelial Cells via Modulation of Unique Sets of Genes Cancer Res., December 1, 2005; 65(23): 10767 - 10775. [Abstract] [Full Text] [PDF]

				N. Oka, S. Nakahara, Y. Takenaka, T. Fukumori, V. Hogan, H.-o. Kanayama, T. Yanagawa, and A. Raz Galectin-3 Inhibits Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand-Induced Apoptosis by Activating Akt in Human Bladder Carcinoma Cells Cancer Res., September 1, 2005; 65(17): 7546 - 7553. [Abstract] [Full Text] [PDF]

				K. H. Ruebel, L. Jin, X. Qian, B. W. Scheithauer, K. Kovacs, N. Nakamura, H. Zhang, A. Raz, and R. V. Lloyd Effects of DNA Methylation on Galectin-3 Expression in Pituitary Tumors Cancer Res., February 15, 2005; 65(4): 1136 - 1140. [Abstract] [Full Text] [PDF]

				E. A. Partridge, C. Le Roy, G. M. Di Guglielmo, J. Pawling, P. Cheung, M. Granovsky, I. R. Nabi, J. L. Wrana, and J. W. Dennis Regulation of Cytokine Receptors by Golgi N-Glycan Processing and Endocytosis Science, October 1, 2004; 306(5693): 120 - 124. [Abstract] [Full Text] [PDF]

				Y. Takenaka, T. Fukumori, T. Yoshii, N. Oka, H. Inohara, H.-R. C. Kim, R. S. Bresalier, and A. Raz Nuclear Export of Phosphorylated Galectin-3 Regulates Its Antiapoptotic Activity in Response to Chemotherapeutic Drugs Mol. Cell. Biol., May 15, 2004; 24(10): 4395 - 4406. [Abstract] [Full Text] [PDF]

				T. Fukumori, Y. Takenaka, T. Yoshii, H.-R. C. Kim, V. Hogan, H. Inohara, S. Kagawa, and A. Raz CD29 and CD7 Mediate Galectin-3-Induced Type II T-Cell Apoptosis Cancer Res., December 1, 2003; 63(23): 8302 - 8311. [Abstract] [Full Text] [PDF]

				C. M. John, H. Leffler, B. Kahl-Knutsson, I. Svensson, and G. A. Jarvis Truncated Galectin-3 Inhibits Tumor Growth and Metastasis in Orthotopic Nude Mouse Model of Human Breast Cancer Clin. Cancer Res., June 1, 2003; 9(6): 2374 - 2383. [Abstract] [Full Text] [PDF]

				T. Yoshii, T. Fukumori, Y. Honjo, H. Inohara, H.-R. C. Kim, and A. Raz Galectin-3 Phosphorylation Is Required for Its Anti-apoptotic Function and Cell Cycle Arrest J. Biol. Chem., February 22, 2002; 277(9): 6852 - 6857. [Abstract] [Full Text] [PDF]

				E. Saggiorato, S. Cappia, P. De Giuli, A. Mussa, G. Pancani, P. Caraci, A. Angeli, and F. Orlandi Galectin-3 as a Presurgical Immunocytodiagnostic Marker of Minimally Invasive Follicular Thyroid Carcinoma J. Clin. Endocrinol. Metab., November 1, 2001; 86(11): 5152 - 5158. [Abstract] [Full Text] [PDF]

				W.-Q. Zhu and J. Ochieng Rapid Release of Intracellular Galectin-3 from Breast Carcinoma Cells by Fetuin Cancer Res., March 1, 2001; 61(5): 1869 - 1873. [Abstract] [Full Text]

				Y. Honjo, P. Nangia-Makker, H. Inohara, and A. Raz Down-Regulation of Galectin-3 Suppresses Tumorigenicity of Human Breast Carcinoma Cells Clin. Cancer Res., March 1, 2001; 7(3): 661 - 668. [Abstract] [Full Text]

				E. A. M. Barboni, S. Bawumia, K. Henrick, and R.C. Hughes Molecular modeling and mutagenesis studies of the N-terminal domains of galectin-3: evidence for participation with the C-terminal carbohydrate recognition domain in oligosaccharide binding Glycobiology, November 1, 2000; 10(11): 1201 - 1208. [Abstract] [Full Text] [PDF]

				N. Mazurek, J. Conklin, J. C. Byrd, A. Raz, and R. S. Bresalier Phosphorylation of the beta -Galactoside-binding Protein Galectin-3 Modulates Binding to Its Ligands J. Biol. Chem., November 10, 2000; 275(46): 36311 - 36315. [Abstract] [Full Text] [PDF]