Galectin-3 - Revision history

Anna Crie: /* Acknowledgements */

2012-01-21T05:47:19Z

Acknowledgements

Vitaly Balan: /* CFG Participating Investigators contributing to the understanding of this paradigm */

2011-09-20T15:04:45Z

CFG Participating Investigators contributing to the understanding of this paradigm

Vitaly Balan at 15:21, 8 September 2011

2011-09-08T15:21:59Z

Vitaly Balan: /* CFG Participating Investigators contributing to the understanding of this paradigm */

2011-09-08T15:17:35Z

CFG Participating Investigators contributing to the understanding of this paradigm

Kurt Drickamer: /* Glycan profiling */

2011-04-15T08:03:30Z

Glycan profiling

Carole Weaver: /* Glycogene microarray */

2011-03-25T23:49:38Z

Glycogene microarray

Kurt Drickamer: /* Biosynthesis of ligands */

2011-03-21T12:12:45Z

Biosynthesis of ligands

Argueso at 19:26, 2 September 2010

2010-09-02T19:26:41Z

Dan Hsu at 16:10, 31 August 2010

2010-08-31T16:10:22Z

Dan Hsu at 15:56, 31 August 2010

2010-08-31T15:56:27Z

← Older revision		Revision as of 05:47, 21 January 2012
Line 180:		Line 180:

	== Acknowledgements ==		== Acknowledgements ==
−	The CFG is grateful to the following PIs for their contributions to this wiki page: Linda Baum, Richard Cummings, Michael Demetriou, Daniel Hsu, Fu-Tong Liu	+	The CFG is grateful to the following PIs for their contributions to this wiki page: Linda Baum, Richard Cummings, Michael Demetriou, Daniel Hsu, Fu-Tong Liu, David F. Smith

@@ Line 20: / Line 20: @@
 == CFG Participating Investigators contributing to the understanding of this paradigm ==
-CFG Participating Investigators (PIs) contributing to the understanding of Galectin-3 include: Pablo Argüeso, Linda Baum, Susan Bellis, Roger Chammas, Richard Cummings, James Dennis, Margaret, Huflejt, Fu-Tong Liu, Joshiah Ochieng, Noorjahan Panjawani, Mauro Perretti, Avraham Raz, James Rini, Maria Roque-Barreira, Sachiko Sato, Tariq Sethi, Irma van Die, Gerardo Vasta, John Wang, Paul Winyard
+CFG Participating Investigators (PIs) contributing to the understanding of Galectin-3 include: Pablo Argüeso, Linda Baum, Susan Bellis, Roger Chammas, Richard Cummings, James Dennis, Margaret, Huflejt, Fu-Tong Liu, Joshiah Ochieng, Noorjahan Panjawani, Mauro Perretti, Avraham Raz, James Rini, Maria Roque-Barreira, Sachiko Sato, Tariq Sethi, Irma van Die, Gerardo Vasta, John Wang, Paul Winyard, Vitaly Balan, Pratima Nangia-Makker
 == Progress toward understanding this GBP paradigm ==

@@ Line 16: / Line 16: @@
 Galectin-3 can oligomerize in the presence of multivalent carbohydrate ligands and is capable of crosslinking glycans on the cell surface, thereby initiating transmembrane signaling events and affecting various cellular functions (reviewed in <ref name="Liu 2005">Liu FT, Rabinovich GA. [http://www.ncbi.nlm.nih.gov/pubmed/15630413 Galectins as modulators of tumour progression.] Nat Rev Cancer. 2005 Jan;5(1):29-41. Review. PubMed PMID: 15630413.</ref><ref>Almkvist J, Karlsson A. [http://www.ncbi.nlm.nih.gov/pubmed/14758082 Galectins as inflammatory mediators.] Glycoconj J.
 ;19(7-9):575-81. Review. PubMed PMID: 14758082.</ref><ref>Ochieng J, Furtak V, Lukyanov P. [http://www.ncbi.nlm.nih.gov/pubmed/14758076 Extracellular functions of galectin-3.] Glycoconj J. 2004;19(7-9):527-35. Review. PubMed PMID: 14758076.</ref>). This ability to self-associate is dependent on the N-terminal region of the protein.
-<br><br>Compared to other galectins, intracellular functions of galectin-3 have been more extensively documented (reviewed in <ref>Liu FT, Patterson RJ, Wang JL. [http://www.ncbi.nlm.nih.gov/pubmed/12223274 Intracellular functions of galectins.] Biochim Biophys Acta. 2002 Sep 19;1572(2-3):263-73. Review. PubMed PMID: 12223274.</ref>). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at serines 6 & 12<ref>Huflejt ME, Turck CW, Lindstedt R, Barondes SH, Leffler H. [http://www.ncbi.nlm.nih.gov/pubmed/8253806 L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine 12 in vivo and by casein kinase I.] J Biol Chem. 1993 Dec 15;268(35):26712-8. PubMed PMID:8253806.</ref>, and tyrosines 79 & 118 by c-Abl<ref>Balan V, Nangia-Makker P, Jang YS, Wang Y, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/20600357 Galectin-3: A novel substrate for c-Abl kinase.] Biochim Biophys Acta. 2010 Jun 30. PubMed PMID: 20600357</ref><ref>Li X, Ma Q, Wang J, Liu X, Yang Y, Zhao H, Wang Y, Jin Y, Zeng J, Li J, Song L, Li X, Li P, Qian X, Cao C. [http://www.ncbi.nlm.nih.gov/pubmed/20150913 c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3.] Cell Death Differ. 2010 Aug;17(8):1277-87. Epub 2010 Feb 12. PubMed PMID: 20150913.</ref>.
+<br><br>Compared to other galectins, intracellular functions of galectin-3 have been more extensively documented (reviewed in <ref>Liu FT, Patterson RJ, Wang JL. [http://www.ncbi.nlm.nih.gov/pubmed/12223274 Intracellular functions of galectins.] Biochim Biophys Acta. 2002 Sep 19;1572(2-3):263-73. Review. PubMed PMID: 12223274.</ref>). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at serines 6 & 12<ref>Huflejt ME, Turck CW, Lindstedt R, Barondes SH, Leffler H. [http://www.ncbi.nlm.nih.gov/pubmed/8253806 L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine 12 in vivo and by casein kinase I.] J Biol Chem. 1993 Dec 15;268(35):26712-8. PubMed PMID:8253806.</ref>, and tyrosines 79,107 & 118 by c-Abl<ref>Balan V, Nangia-Makker P, Jang YS, Wang Y, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/20600357 Galectin-3: A novel substrate for c-Abl kinase.] Biochim Biophys Acta. 2010 Jun 30. PubMed PMID: 20600357</ref><ref>Li X, Ma Q, Wang J, Liu X, Yang Y, Zhao H, Wang Y, Jin Y, Zeng J, Li J, Song L, Li X, Li P, Qian X, Cao C. [http://www.ncbi.nlm.nih.gov/pubmed/20150913 c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3.] Cell Death Differ. 2010 Aug;17(8):1277-87. Epub 2010 Feb 12. PubMed PMID: 20150913.</ref>.
@@ Line 164: / Line 164: @@
 === Glycogene microarray ===
 Gene expression analyses have been performed on several cell types and tissues at [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=galectin-3&cat=coree Core E] of the CFG. Probes for human galectin-3 have been included in all versions of the CFG glycogene chip, and probes for mouse galectin-3 are included on versions 2, 3, and 4.
 <br>

@@ Line 20: / Line 20: @@
 == CFG Participating Investigators contributing to the understanding of this paradigm ==
-CFG Participating Investigators (PIs) contributing to the understanding of Galectin-3 include: Pablo Argüeso, Linda Baum, Susan Bellis, Roger Chammas, Richard Cummings, James Dennis, Margaret, Huflejt, Fu-Tong Liu, Joshiah Ochieng, Noorjahan Panjawani, Mauro Perretti, Avram Raz, James Rini, Maria Roque-Barreira, Sachiko Sato, Tariq Sethi, Irma van Die, Gerardo Vasta, John Wang, Paul Winyard
+CFG Participating Investigators (PIs) contributing to the understanding of Galectin-3 include: Pablo Argüeso, Linda Baum, Susan Bellis, Roger Chammas, Richard Cummings, James Dennis, Margaret, Huflejt, Fu-Tong Liu, Joshiah Ochieng, Noorjahan Panjawani, Mauro Perretti, Avraham Raz, James Rini, Maria Roque-Barreira, Sachiko Sato, Tariq Sethi, Irma van Die, Gerardo Vasta, John Wang, Paul Winyard
 == Progress toward understanding this GBP paradigm ==

@@ Line 161: / Line 161: @@
 === Glycan profiling ===
 <br>
 === Glycogene microarray ===
 Gene expression analyses have been performed on several cell types and tissues at [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=galectin-3&cat=coree Core E] of the CFG. Probes for human galectin-3 have been included in all versions of the CFG glycogene chip, and probes for mouse galectin-3 are included on versions 2, 3, and 4.

@@ Line 31: / Line 31: @@
 <br>
 === Biosynthesis of ligands ===
 === Structure ===
 The structures of the CRD of galectin-3 from X-ray crystallographic<ref>Seetharaman, J., Kanigsberg, A., Slaaby, R., Leffler, H., Barondes, S.H., and Rini, J.M. [http://www.ncbi.nlm.nih.gov/pubmed/9582341 X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1 angstrom resolution.] J. Biol. Chem. 1998; 273: 13047–13052. PMID: 9582341.</ref> and NMR<ref>Umemoto K, Leffler H, Venot A, Valafar H, Prestegard JH. [http://www.ncbi.nlm.nih.gov/pubmed/12667058 Conformational differences in liganded and unliganded states of Galectin-3.] Biochem. 2003;  8;42(13):3688-3695. PMID: 12667058.</ref> analyses have been described. The proline-rich N-terminal domain is required for oligomerization of galectin-3<ref>Hsu DK, Zuberi RI, Liu FT. [http://www.ncbi.nlm.nih.gov/pubmed/1629216 Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin.] J Biol Chem. 1992; 267(20):14167-14174. PMID: 1629216.</ref> and demonstrates significant interaction with the CRD as initially suggested by observations that a monoclonal antibody recognizing an epitope in the N-terminus was capable of inhibiting glycan binding in the C-terminal CRD<ref>Liu FT, Hsu DK, Zuberi RI, Hill PN, Shenhav A, Kuwabara I, Chen SS. [http://www.ncbi.nlm.nih.gov/pubmed/8634249 Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains.] Biochemistry. 1996; 35(19):6073-6079. PMID: 8634249.</ref>, and revealed by NMR and EM studies<ref>Birdsall B, Feeney J, Burdett ID, Bawumia S, Barboni EA, Hughes RC. [http://www.ncbi.nlm.nih.gov/pubmed/11294654 NMR solution studies of hamster galectin-3 and electron microscopic visualization of surface-adsorbed complexes: evidence for interactions between the N- and C-terminal domains.] Biochem. 2001; 40:4859-4866. PMID: 11294654.</ref>.

@@ Line 28: / Line 28: @@
 <br>
 === Cellular expression of GBP and ligands===
+Galectin-3 is constitutively expressed in epithelial and myeloid cells, and regulated by processes that include cell proliferation, inflammation, and tumor initiation and progression[cite]. Gene expression in various cells and tissues have been performed with CFG [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=galectin-3&cat=coree Core IgE].
 <br>
 === Biosynthesis of ligands ===
@@ Line 34: / Line 34: @@
 <br>
 === Structure ===
+The structures of the CRD of galectin-3 from X-ray crystallographic<ref>Seetharaman, J., Kanigsberg, A., Slaaby, R., Leffler, H., Barondes, S.H., and Rini, J.M. [http://www.ncbi.nlm.nih.gov/pubmed/9582341 X-ray crystal structure of the human galectin-3 carbohydrate recognition domain at 2.1 angstrom resolution.] J. Biol. Chem. 1998; 273: 13047–13052. PMID: 9582341.</ref> and NMR<ref>Umemoto K, Leffler H, Venot A, Valafar H, Prestegard JH. [http://www.ncbi.nlm.nih.gov/pubmed/12667058 Conformational differences in liganded and unliganded states of Galectin-3.] Biochem. 2003;  8;42(13):3688-3695. PMID: 12667058.</ref> analyses have been described. The proline-rich N-terminal domain is required for oligomerization of galectin-3<ref>Hsu DK, Zuberi RI, Liu FT. [http://www.ncbi.nlm.nih.gov/pubmed/1629216 Biochemical and biophysical characterization of human recombinant IgE-binding protein, an S-type animal lectin.] J Biol Chem. 1992; 267(20):14167-14174. PMID: 1629216.</ref> and demonstrates significant interaction with the CRD as initially suggested by observations that a monoclonal antibody recognizing an epitope in the N-terminus was capable of inhibiting glycan binding in the C-terminal CRD<ref>Liu FT, Hsu DK, Zuberi RI, Hill PN, Shenhav A, Kuwabara I, Chen SS. [http://www.ncbi.nlm.nih.gov/pubmed/8634249 Modulation of functional properties of galectin-3 by monoclonal antibodies binding to the non-lectin domains.] Biochemistry. 1996; 35(19):6073-6079. PMID: 8634249.</ref>, and revealed by NMR and EM studies<ref>Birdsall B, Feeney J, Burdett ID, Bawumia S, Barboni EA, Hughes RC. [http://www.ncbi.nlm.nih.gov/pubmed/11294654 NMR solution studies of hamster galectin-3 and electron microscopic visualization of surface-adsorbed complexes: evidence for interactions between the N- and C-terminal domains.] Biochem. 2001; 40:4859-4866. PMID: 11294654.</ref>.
 <br>
 === Biological roles of GBP-ligand interaction ===
@@ Line 160: / Line 160: @@
 === Glycan profiling ===
+Glycan recognition analyses have been performed by [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=galectin-3&cat=coreh Core H] of the CFG.
 <br>
 === Glycogene microarray ===
+Gene expression analyses have been performed on several cell types and tissues at [http://www.functionalglycomics.org/glycomics/search/jsp/result.jsp?query=galectin-3&cat=coree Core E] of the CFG.
 <br>
 === Knockout mouse lines ===
-Galectin-3 knockout mice were [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotyped] by the CFG and continue to be used by investigators to study the biological functions of Galectin-3.
+Galectin-3 knockout mice were [https://www.functionalglycomics.org/glycomics/publicdata/phenotyping.jsp phenotyped by Core G] of the CFG and continue to be used by investigators to study the biological functions of Galectin-3.
 === Glycan array ===

@@ Line 5: / Line 5: @@
 * has unique functions intra- and extra-cellularly, due to an unusual N-terminal domain that can participate in protein-protein interactions
 * has a unique mode of multimerization
-* is the only known anti-apoptotic galectin, and acts through intracellular action<ref>Saegusa J, Hsu DK, Liu W, Kuwabara I, Kuwabara Y, Yu L, Liu FT [http://www.ncbi.nlm.nih.gov/pubmed/18463681 Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation.] J Invest Dermatol. 2008 Oct;128(10):2403-11.</ref>
+* is the only known anti-apoptotic galectin, and acts through intracellular action<ref>Saegusa J, Hsu DK, Liu W, Kuwabara I, Kuwabara Y, Yu L, Liu FT [http://www.ncbi.nlm.nih.gov/pubmed/18463681 Galectin-3 protects keratinocytes from UVB-induced apoptosis by enhancing AKT activation and suppressing ERK activation.] J Invest Dermatol. 2008 Oct;128(10):2403-11. PubMed PMID: 18463681; PubMed Central PMCID: PMC2768377.</ref>
 * null mice have distinct phenotypes, including alterations in inflammatory and wound-healing responses, and cyst formation in disease<ref>Chiu MG, Johnson TM, Woolf AS, Dahm-Vicker EM, Long DA, Guay-Woodford L,
 Hillman KA, Bawumia S, Venner K, Hughes RC, Poirier F, Winyard PJ. [http://www.ncbi.nlm.nih.gov/pubmed/17148658 Galectin-3 associates with the primary cilium and modulates cyst growth in congenital polycystic kidney disease.] Am J Pathol. 2006 Dec;169(6):1925-38.</ref>
@@ Line 16: / Line 16: @@
 Galectin-3 can oligomerize in the presence of multivalent carbohydrate ligands and is capable of crosslinking glycans on the cell surface, thereby initiating transmembrane signaling events and affecting various cellular functions (reviewed in <ref name="Liu 2005">Liu FT, Rabinovich GA. [http://www.ncbi.nlm.nih.gov/pubmed/15630413 Galectins as modulators of tumour progression.] Nat Rev Cancer. 2005 Jan;5(1):29-41. Review. PubMed PMID: 15630413.</ref><ref>Almkvist J, Karlsson A. [http://www.ncbi.nlm.nih.gov/pubmed/14758082 Galectins as inflammatory mediators.] Glycoconj J.
 ;19(7-9):575-81. Review. PubMed PMID: 14758082.</ref><ref>Ochieng J, Furtak V, Lukyanov P. [http://www.ncbi.nlm.nih.gov/pubmed/14758076 Extracellular functions of galectin-3.] Glycoconj J. 2004;19(7-9):527-35. Review. PubMed PMID: 14758076.</ref>). This ability to self-associate is dependent on the N-terminal region of the protein.
-<br><br>Compared to other galectins, intracellular functions of galectin-3 have been more extensively documented (reviewed in <ref>Liu FT, Patterson RJ, Wang JL. [http://www.ncbi.nlm.nih.gov/pubmed/12223274 Intracellular functions of galectins.] Biochim Biophys Acta. 2002 Sep 19;1572(2-3):263-73. Review. PubMed PMID: 12223274.</ref>). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at serines 6 & 12<ref>Huflejt ME, Turck CW, Lindstedt R, Barondes SH, Leffler H. [http://www.ncbi.nlm.nih.gov/pubmed/8253806 L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine 12 in vivo and by casein kinase I.] J Biol Chem. 1993 Dec 15;268(35):26712-8. PubMed PMID:8253806.</ref>, and tyrosines 79 & 118 by c-Abl<ref>Balan V, Nangia-Makker P, Jang YS, Wang Y, Raz A. Galectin-3: A novel
+<br><br>Compared to other galectins, intracellular functions of galectin-3 have been more extensively documented (reviewed in <ref>Liu FT, Patterson RJ, Wang JL. [http://www.ncbi.nlm.nih.gov/pubmed/12223274 Intracellular functions of galectins.] Biochim Biophys Acta. 2002 Sep 19;1572(2-3):263-73. Review. PubMed PMID: 12223274.</ref>). In some cases, intracellular proteins with which the protein interacts and which possibly mediate these functions have been identified. Galectin-3 can be phosphorylated at serines 6 & 12<ref>Huflejt ME, Turck CW, Lindstedt R, Barondes SH, Leffler H. [http://www.ncbi.nlm.nih.gov/pubmed/8253806 L-29, a soluble lactose-binding lectin, is phosphorylated on serine 6 and serine 12 in vivo and by casein kinase I.] J Biol Chem. 1993 Dec 15;268(35):26712-8. PubMed PMID:8253806.</ref>, and tyrosines 79 & 118 by c-Abl<ref>Balan V, Nangia-Makker P, Jang YS, Wang Y, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/20600357 Galectin-3: A novel substrate for c-Abl kinase.] Biochim Biophys Acta. 2010 Jun 30. PubMed PMID: 20600357</ref><ref>Li X, Ma Q, Wang J, Liu X, Yang Y, Zhao H, Wang Y, Jin Y, Zeng J, Li J, Song L, Li X, Li P, Qian X, Cao C. [http://www.ncbi.nlm.nih.gov/pubmed/20150913 c-Abl and Arg tyrosine kinases regulate lysosomal degradation of the oncoprotein Galectin-3.] Cell Death Differ. 2010 Aug;17(8):1277-87. Epub 2010 Feb 12. PubMed PMID: 20150913.</ref>.
@@ Line 143: / Line 142: @@
 Galectin-3 expression is altered in a variety of tumors in comparison to normal tissues<ref>Danguy A, Camby I, Kiss R. [http://www.ncbi.nlm.nih.gov/pubmed/12223276 Galectins and cancer.] Biochim Biophys Acta. 2002 Sep 19;1572(2-3):285-93. Review. PubMed PMID: 12223276.</ref>. The diagnostic utility of Galectin-3 expression in thyroid cancer has been extensively demonstrated (e.g., <ref>Chiu CG, Strugnell SS, Griffith OL, Jones SJ, Gown AM, Walker B, Nabi IR, Wiseman SM. [http://www.ncbi.nlm.nih.gov/pubmed/20363921 Diagnostic utility of galectin-3 in thyroid cancer.] Am J Pathol. 2010 May;176(5):2067-81. Epub 2010 Apr 2. PubMed PMID: 20363921; PubMed Central PMCID: PMC2861072.</ref><ref>Carpi A, Mechanick JI, Saussez S, Nicolini A. [http://www.ncbi.nlm.nih.gov/pubmed/20578236 Thyroid tumor marker genomics and proteomics: diagnostic and clinical implications.] J Cell Physiol. 2010 Sep;224(3):612-9. PubMed PMID: 20578236.</ref>). The role of Galectin-3 in tumor growth, progression, and metastasis has been comprehensively documented (reviewed in <ref name="Liu 2005"/>). There is evidence that Galectin-3 expression is necessary for the initiation of the transformed phenotype of tumors, possibly related to its ability to interact with oncogenic K-Ras<ref>Shalom-Feuerstein R, Plowman SJ, Rotblat B, Ariotti N, Tian T, Hancock JF, Kloog Y. [http://www.ncbi.nlm.nih.gov/pubmed/18701484 K-ras nanoclustering is subverted by overexpression of the scaffold protein galectin-3.] Cancer Res. 2008 Aug 15;68(16):6608-16. PubMed PMID: 18701484; PubMed Central PMCID: PMC2587079.</ref>. <br>
-The most extensively studied function of Galectin-3 is its inhibition of apoptosis in a range of tumor cell types exposed to diverse apoptotic stimuli (reviewed in <ref>Yang RY, Rabinovich GA, Liu FT. [http://www.ncbi.nlm.nih.gov/pubmed/18549522 Galectins: structure, function and therapeutic potential.] Expert Rev Mol Med. 2008 Jun 13;10:e17. Review. PubMed PMID: 18549522.</ref>). The mechanism by which Galectin-3 inhibits apoptosis in tumor cells has been extensively studied <ref name="Liu 2005"/><ref>Nakahara S, Oka N, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/15843888 On the role of galectin-3 in cancer apoptosis.] Apoptosis. 2005; 10:267-75. PubMed PMID: 15843888.</ref>). Apoptosis induced by the tumor suppressor p53 involves repression of Galectin-3<ref>Cecchinelli B, et al. [http://www.ncbi.nlm.nih.gov/pubmed/16738336 Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis.] Mol Cell Biol. 2006; 26:4746-57. PubMed PMID: 16738336.</ref>. <br>
+The most extensively studied function of Galectin-3 is its inhibition of apoptosis in a range of tumor cell types exposed to diverse apoptotic stimuli (reviewed in <ref>Yang RY, Rabinovich GA, Liu FT. [http://www.ncbi.nlm.nih.gov/pubmed/18549522 Galectins: structure, function and therapeutic potential.] Expert Rev Mol Med. 2008 Jun 13;10:e17. Review. PubMed PMID: 18549522.</ref>). The mechanism by which Galectin-3 inhibits apoptosis in tumor cells has been extensively studied <ref name="Liu 2005"/><ref>Nakahara S, Oka N, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/15843888 On the role of galectin-3 in cancer apoptosis.] Apoptosis. 2005; 10:267-75. PubMed PMID: 15843888.</ref>). Apoptosis induced by the tumor suppressor p53 involves repression of Galectin-3<ref>Cecchinelli B, et al. [http://www.ncbi.nlm.nih.gov/pubmed/16738336 Repression of the antiapoptotic molecule galectin-3 by homeodomain-interacting protein kinase 2-activated p53 is required for p53-induced apoptosis.] Mol Cell Biol. 2006; 26:4746-57. PubMed PMID: 16738336; PMCID: PubMed Central PMC1489111</ref>. <br>
 Endogenous galectin-3 promotes tumor cell growth (reviewed in <ref name="Liu 2005"/>), one mechanism may involve interaction with transcription factors<ref>Paron I, et al. [http://www.ncbi.nlm.nih.gov/pubmed/12615069 Nuclear localization of Galectin-3 in transformed thyroid cells: a role in transcriptional regulation.] Biochem Biophys Res Commun. 2003; 302:545-53. PubMed PMID: 12615069.</ref>, another may be facilitation of the signaling of K-Ras to Raf and PI3 kinase<ref>Ashery U, et al. [http://www.ncbi.nlm.nih.gov/pubmed/16691442 Spatiotemporal organization of Ras signaling: rasosomes and the galectin switch.] Cell Mol Neurobiol. 2006; 26:471-95. PubMed PMID: 16691442.</ref>. Endogenous galectin-3 also regulates tumor progression by influencing cell cycling; its binds to β-catenin and stimulates the expression of cyclin D and c-Myc<ref>Shimura T, Takenaka Y, Tsutsumi S, Hogan V, Kikuchi A, Raz A. [http://www.ncbi.nlm.nih.gov/pubmed/15374939 Galectin-3, a novel binding partner of beta-catenin.] Cancer Res. 2004; 64:6363-7. PubMed PMID: 15374939.</ref>. <br>
-Galectin-3 can affect tumor metastasis by exerting its effect in the tumor microenvironment, including angiogenesis and fibrosis<ref name="Liu 2005"/>. Galectin-3 plays a role in activation of myofibroblasts in the liver and contributes to liver fibrosis induced by carbon tetrachloride<ref>Henderson NC, et al. [http://www.ncbi.nlm.nih.gov/pubmed/16549783 Galectin-3 regulates myofibroblast activation and hepatic fibrosis.] Proc Natl Acad Sci U S A. 2006; 103:5060-5. PubMed PMID: 16549783.</ref>.<br>
+Galectin-3 can affect tumor metastasis by exerting its effect in the tumor microenvironment, including angiogenesis and fibrosis<ref name="Liu 2005"/>. Galectin-3 plays a role in activation of myofibroblasts in the liver and contributes to liver fibrosis induced by carbon tetrachloride<ref>Henderson NC, et al. [http://www.ncbi.nlm.nih.gov/pubmed/16549783 Galectin-3 regulates myofibroblast activation and hepatic fibrosis.] Proc Natl Acad Sci U S A. 2006; 103:5060-5. PubMed PMID: 16549783; PubMed Central PMCID: PMC1458794.</ref>.<br>
 In a human melanoma tumor model in immunodeficient mice, administration of galectin-3 results in suppressing the tumor killing effect of tumor-reactive T cells<ref>Peng W, Wang HY, Miyahara Y, Peng G, Wang RF. [http://www.ncbi.nlm.nih.gov/pubmed/18757439 Tumor-associated galectin-3 modulates the function of tumor-reactive T cells.] Cancer Res. 2008 Sep 1;68(17):7228-36. PubMed PMID: 18757439.</ref>. Tumor-associated galectin-3 may also contribute to tumor immune escape by rendering tumor-infiltrating cytolytic lymphocytes anergic<ref>Demotte N, Stroobant V, Courtoy PJ, Van Der Smissen P, Colau D, Luescher IF, Hivroz C, Nicaise J, Squifflet JL, Mourad M, Godelaine D, Boon T, van der Bruggen P. [http://www.ncbi.nlm.nih.gov/pubmed/18342010 Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.] Immunity. 2008 Mar;28(3):414-24. PubMed PMID: 18342010.</ref>.<br>
-Galectin-3 affects the motility of tumor cells and influences their invasiveness in vitro. However, both positive and negative effects have been reported<ref>Le Marer N, Hughes RC. [http://www.ncbi.nlm.nih.gov/pubmed/8647922 Effects of the carbohydrate-binding protein galectin-3 on the invasiveness of human breast carcinoma cells.] J Cell Physiol. 1996; 168:51-8. PubMed PMID: 8647922.</ref><ref>Moisa A, et al. [http://www.ncbi.nlm.nih.gov/pubmed/17695496 Growth/adhesion-regulatory tissue lectin galectin-3: stromal presence but not cytoplasmic/nuclear expression in tumor cells as a negative prognostic factor in breast cancer.] Anticancer Res. 2007; 27:2131-9. PubMed PMID: 17695496.</ref>. Endogenous galectin-3 can also contribute to cell motility and in vitro invasiveness<ref>Matarrese P, et al. [http://www.ncbi.nlm.nih.gov/pubmed/10699929 Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties.] Int J Cancer. 2000; 85:545-54. PubMed PMID: 10699929.</ref><ref>O'Driscoll L, Linehan R, Liang YH, Joyce H, Oglesby I, Clynes M. [http://www.ncbi.nlm.nih.gov/pubmed/12530054 Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro.] Anticancer Res. 2002; 22:3117-25. PubMed PMID: 12530054.</ref><ref>Shimura T, et al. [http://www.ncbi.nlm.nih.gov/pubmed/15867344 Implication of galectin-3 in Wnt signaling.] Cancer Res. 2005; 65:3535-7. PubMed PMID: 15867344.</ref>. Galectin-3 has angiogenic activity, which may be related to its ability to induce migration of endothelial cells<ref>Nangia-Makker P, et al. [http://www.ncbi.nlm.nih.gov/pubmed/10702407 Galectin-3 induces endothelial cell morphogenesis and angiogenesis.] Am J Pathol. 2000; 156:899-909. PubMed PMID: 10702407.</ref>.<br>
+Galectin-3 affects the motility of tumor cells and influences their invasiveness in vitro. However, both positive and negative effects have been reported<ref>Le Marer N, Hughes RC. [http://www.ncbi.nlm.nih.gov/pubmed/8647922 Effects of the carbohydrate-binding protein galectin-3 on the invasiveness of human breast carcinoma cells.] J Cell Physiol. 1996; 168:51-8. PubMed PMID: 8647922.</ref><ref>Moisa A, et al. [http://www.ncbi.nlm.nih.gov/pubmed/17695496 Growth/adhesion-regulatory tissue lectin galectin-3: stromal presence but not cytoplasmic/nuclear expression in tumor cells as a negative prognostic factor in breast cancer.] Anticancer Res. 2007; 27:2131-9. PubMed PMID: 17695496.</ref>. Endogenous galectin-3 can also contribute to cell motility and in vitro invasiveness<ref>Matarrese P, et al. [http://www.ncbi.nlm.nih.gov/pubmed/10699929 Galectin-3 overexpression protects from apoptosis by improving cell adhesion properties.] Int J Cancer. 2000; 85:545-54. PubMed PMID: 10699929.</ref><ref>O'Driscoll L, Linehan R, Liang YH, Joyce H, Oglesby I, Clynes M. [http://www.ncbi.nlm.nih.gov/pubmed/12530054 Galectin-3 expression alters adhesion, motility and invasion in a lung cell line (DLKP), in vitro.] Anticancer Res. 2002; 22:3117-25. PubMed PMID: 12530054.</ref><ref>Shimura T, et al. [http://www.ncbi.nlm.nih.gov/pubmed/15867344 Implication of galectin-3 in Wnt signaling.] Cancer Res. 2005; 65:3535-7. PubMed PMID: 15867344.</ref>. Galectin-3 has angiogenic activity, which may be related to its ability to induce migration of endothelial cells<ref>Nangia-Makker P, et al. [http://www.ncbi.nlm.nih.gov/pubmed/10702407 Galectin-3 induces endothelial cell morphogenesis and angiogenesis.] Am J Pathol. 2000; 156:899-909. PubMed PMID: 10702407; PubMed Central PMCID: PMC1876842.</ref>.<br>
 Studies with animal models have provided evidence for the role of galectins in tumor metastasis in vivo (reviewed in <ref name="Liu 2005"/>). For example, liver metastases of human adenocarcinoma xenotransplants in SCID mice are inhibitable by anti-galectin-3 antibody. Breast carcinoma cells overexpressing transgenic galectin-3 have higher metastatic potential. In an orthotopic nude mouse model of human breast cancer, tumor metastasis is inhibitable by C-terminal domain fragment of galectin-3 (galectin-3C)<ref>John CM, Leffler H, Kahl-Knutsson B, Svensson I, Jarvis GA. [http://www.ncbi.nlm.nih.gov/pubmed/12796408 Truncated galectin-3 inhibits tumor growth and metastasis in orthotopic nude mouse model of human breast cancer.] Clin Cancer Res. 2003; 9:2374-83. PubMed PMID: 12796408.</ref>.<br>
-Galectin-3 contributes to chemotherapeutic resistance of thyroid cancer cells in vitro, the progression of disease in prostate cancer<ref>Wang Y, et al. [http://www.ncbi.nlm.nih.gov/pubmed/19286570 Regulation of prostate cancer progression by galectin-3.] Am J Pathol. 2009; 174:1515-23. PubMed PMID: 19286570.</ref> and development of carcinogen-induced lung tumorigenesis<ref>Abdel-Aziz HO, et al. [http://www.ncbi.nlm.nih.gov/pubmed/18204863 Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray study.] J Cancer Res Clin Oncol. 2008; 134:777-88. PubMed PMID: 18204863.</ref> in mouse models. However, the absence of galectin-3 may not affect the evolution of cancers<ref>Eude-Le Parco I, et al. [http://www.ncbi.nlm.nih.gov/pubmed/18849326 Genetic assessment of the importance of galectin-3 in cancer initiation, progression, and dissemination in mice.] Glycobiology. 2009; 19:68-75. PubMed PMID: 18849326.</ref>. Galectin-3-targeting small molecule inhibitors enhancs apoptosis induced by chemo- and radio-therapy in papillary thyroid cancer in vitro<ref>Lin CI, et al. [http://www.ncbi.nlm.nih.gov/pubmed/19825987 Galectin-3 targeted therapy with a small molecule inhibitor activates apoptosis and enhances both chemosensitivity and radiosensitivity in papillary thyroid cancer.] Mol Cancer Res. 2009; 7:1655-62. PubMed PMID: 19825987.</ref>. GCS-100, a galectin-3 antagonist, induces myeloma cell death in vitro<ref>Streetly MJ, Maharaj L, Joel S, Schey SA, Gribben JG, Cotter FE. [http://www.ncbi.nlm.nih.gov/pubmed/20190189 GCS-100, a novel galectin-3 antagonist, modulates MCL-1, NOXA, and cell cycle to induce myeloma cell death.] Blood. 2010; 115:3939-48. PubMed PMID: 20190189.</ref>). <br>
+Galectin-3 contributes to chemotherapeutic resistance of thyroid cancer cells in vitro, the progression of disease in prostate cancer<ref>Wang Y, et al. [http://www.ncbi.nlm.nih.gov/pubmed/19286570 Regulation of prostate cancer progression by galectin-3.] Am J Pathol. 2009; 174:1515-23. PubMed PMID: 19286570; PubMed Central PMCID: PMC2671381.</ref> and development of carcinogen-induced lung tumorigenesis<ref>Abdel-Aziz HO, et al. [http://www.ncbi.nlm.nih.gov/pubmed/18204863 Targeted disruption of the galectin-3 gene results in decreased susceptibility to NNK-induced lung tumorigenesis: an oligonucleotide microarray study.] J Cancer Res Clin Oncol. 2008; 134:777-88. PubMed PMID: 18204863.</ref> in mouse models. However, the absence of galectin-3 may not affect the evolution of cancers<ref>Eude-Le Parco I, et al. [http://www.ncbi.nlm.nih.gov/pubmed/18849326 Genetic assessment of the importance of galectin-3 in cancer initiation, progression, and dissemination in mice.] Glycobiology. 2009; 19:68-75. PubMed PMID: 18849326.</ref>. Galectin-3-targeting small molecule inhibitors enhancs apoptosis induced by chemo- and radio-therapy in papillary thyroid cancer in vitro<ref>Lin CI, et al. [http://www.ncbi.nlm.nih.gov/pubmed/19825987 Galectin-3 targeted therapy with a small molecule inhibitor activates apoptosis and enhances both chemosensitivity and radiosensitivity in papillary thyroid cancer.] Mol Cancer Res. 2009; 7:1655-62. PubMed PMID: 19825987.</ref>. GCS-100, a galectin-3 antagonist, induces myeloma cell death in vitro<ref>Streetly MJ, Maharaj L, Joel S, Schey SA, Gribben JG, Cotter FE. [http://www.ncbi.nlm.nih.gov/pubmed/20190189 GCS-100, a novel galectin-3 antagonist, modulates MCL-1, NOXA, and cell cycle to induce myeloma cell death.] Blood. 2010; 115:3939-48. PubMed PMID: 20190189.</ref>). <br>
 == CFG resources used in investigations ==