{"references": ["Taylor ME, Drickamer K, Schnaar RL, Etzler ME, Varki A. Discovery and Classification of Glycan- Binding Proteins. In: Varki A, Cummings RD, Esko JD, et al. Essentials of Glycobiology [Internet]. Coid Spring Harbor; 2015-2017; Chapter 28.", "Lam SK, Ng TB. Lectins: production and practical applications. Appl Microbio! Biotechnol 2011; 89(1): 45-55.", "GalectinTherapeutics\u00a9 website. (Accessed on December 1, 2017).", "Ebrahim AH, Alalawi Z, Mir\u00e1ndola L, Rakhshanda R, Dahlbeck S, Nguyen D, et al. Galectins in c\u00e1ncer: carcinogenesis, diagnosis and therapy. Ann Tran Med 2014; 2(9): 88.", "Thijssen VL, Heusschen R, Caers J, Griffioen, AW. Galectin expression in c\u00e1ncer diagnosis and prognosis: A systematic review. Biochim Biophys Acta 2015; 1855 (2): 235-247.", "Cummings RD, Liu FT, Vasta GR. Galectins. In: Varki A, Cummings RD, Esko JD, et al., editors. Essentials of Glycobiology [Internet]. Coid Spring Harbor, 2015-2017; Chapter 36.", "HUGO Gene Nomenclatura Committee at the European Bioinformatics Institute website. (Accessed on December 1, 2017).", "Than NG, Romero R, Erez O, Weckle A, Tarca AL, Hotra J, et al. Emergence of hormonal and redox regulation of galectin-1 in placental mammals: implication \u00a1n maternal-fetal \u00a1mmune tolerance. Proc Nati Acad Sci 2008; 105(41): 15819-24.", "Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z, Xu Y, et al. A primate subfamily of galectins expressed at the maternal-fetal interface that promote immune cell death. Proc Nati Acad Sci 2009; 106(24):9731-6.", "The UniProt Consortium. UniProt: the universal protein knowledgebase. Nucleic Acids Res 2017; 45: D158-D169. (Accessed on December 15, 2017).", "von Wolff M, Wang X, Gabius HJ, Strowitzki, T. Galectin fingerprinting in human endometrium and decidua during the menstrual cycle and in early gestation. Mol Hum Reprod 2005; 11(3): 189-94.", "Jeschke U, Hutter S, Heublein S, Vrekoussis T, Andergassen U, Unverdorben L, et al. Expression and function of galectins in the endometrium and at the human feto-maternal interface. Placenta 2013; 34(10):863-72.", "Hokama A, Mizoguchi E, Mizoguchi A. Roles of galectins in inflammatory bowel disease. World J Gastroenterol 2008; 14(33):5133-7.", "Than NG, Romero R, Goodman M, Weckle A, Xing J, Dong Z. A primate subfamily of galectins expressed at the maternal-fetal interface that promote \u00a1mmune cell death. Proc Nati Acad Sci 2009; 106(24):9731-6.", "Cao ZQ, Guo XL. The role of galectin-4 in physiology and diseases. Protein Cell 2016; 7(5): 314-324.", "Gendronneau G, Sidhu SS, Delacour D, Dang T, Calonne C,Houzelstein D, et al. Galectin-7 in the Control of Epidermal Homeostasis after Injury. Mol Biol Cell 2008; 19(12): 5541-5549.", "Heusschen R, Freitag N, Tirado-Gonzalez I, Barrientes G, Moschansky P, Munoz-Fernandez R, et al. Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnaney. Biol Reprod 2013; 88(1):22.", "Heusschen R, Schulkens IA, van Beijnum J, Griffioen AW, Thijssen VL. Endothelial LGALS9 splice variant expression in endothelial cell biology and angiogenesis. Biochim Biophys Acta 2014; 1842(2): 284-92.", "Li YH, Zhou WH, Tao Y, Wang SC, Jiang YL, Zhang D, et al. The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnaney. Cell Mol Immunol 2016; 13(1):73-81.", "Chua JC, Douglass JA, Gillman A, O'Hehir RE, Meeusen EN. Galectin-10, a potential biomarker of eosinophilic airway inflammation. PLoS ONE 2012;7(8):e42549.", "Hughes RC. Secretion of the galectin family of mammalian carbohydrate-binding proteins. Biochim Biophys Acta 1999; 1473 (1): 172-185.", "Hern\u00e1ndez JD, Baum LG. Ah, sweet mystery of death! Galectins and control of cell fate. Glycobiology 2002; 12(10): 127R-36R.", "Fuster MM, Esko JD. The sweet and sour of c\u00e1ncer: Glycans as novel therapeutic targets. Nat Rev C\u00e1ncer 2005; 5(7): 526-42.", "Heusschen R, Griffioen AW, Thijssen VL. Galectin-9 in tumor biology: A jack of m\u00faltiple trades. Biochim Biophys Acta 2013; 1836(1): 177-85.", "Vladoiu MC, Labrie M, St-Pierre Y. Intracellular galectins in c\u00e1ncer cells: Potential new targets for therapy. Int J Oncol 2014; 44(4): 1001-14.", "Dumic J, Dabelic S, Fl\u00f3gel M. Galectin-3: an open-ended story. Biochim Biophys Acta 2006;1760(4): 616-35.", "Hafiz A, AISadek DM, Galectin-3 as a Potential Target to Prevent C\u00e1ncer Met\u00e1stasis. Clin Med Insights Oncol 2015; 25(9): 113-21.", "ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT02575404, GR-MD-02 Plus Pembrolizumab in Melanoma, Non-small Cell Lung C\u00e1ncer, and Squamous Cell Head and Neck C\u00e1ncer Patients; 2015. [cited 2017 Dec 12]", "ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). Identifier NCT02117362, Galectin Inhibitor (GR-MD-02) and Ipilimumab in Patients With Metastatic Melanoma; 2014. [cited 2017 Dec 12]", "Wada 1, Kanwar Y.S. Identification and characterization of galectin-9, a novel 0- galactoside-binding mammalian lectin. J. Biol. Chem. 1997; 272(9): 6078-86.", "Wada J, Ota K, Kumar A, Wallner El, Kanwar YS. Developmental regulation, expression, and apoptotic potential of galectin-9, a 0-galactoside binding lectin. J Clin Investig 1997; 99(10): 2452-61.", "Leal-Pinto E, Tao W., Rappaport J, Richardson M, Knorr BA, Abramson RG. Molecular cloning and functional reconstitution of a urate transporter/channel. J Biol Chem 1997; 272(1): 617-25.", "Lipkowitz MS, Leal-Pinto E, Rappoport JZ, Najfeld V, Abramson RG. Functional reconstitution, membrane targeting, genomic structure, and chromosomal localization of a human urate transporter. J Clin Investig 2001; 107(9): 1103-15.", "Tsuboi Y, Abe H, Nakagawa R, Oomizu S, Watanabe K, Nishi N, Nakamura T, et al. Galectin-9 protects mice from the Shwartzman reaction by attracting prostaglandin E2- producing polymorphonuclear leukocytes. Clin Immunol 2007; 124(2):221-33.", "Spitzenberger F, Graessler J, Schroeder HE. Molecular and functional characterization of galectin 9 mRNA isoforms in porcine and human cells and tissues. Biochimie 2001; 83(9):851-62.", "Thijssen VL, Hulsmans S, Griffioen AW. The galectin profile of the endothelium: Altered expression and localization in activated and tumor endothelial cells. Am J Pathol 2008; 172(2): 545-53.", "Asakura H, Kashio Y, Nakamura K, Seki M, Dai S, Shirato Y, et al. Selectivo eosinophil adhesi\u00f3n to fibroblast via IFN-y-induced galectin-9. J Immunol 2002; 169 (10) 5912-18.", "Tureci O, Schmitt H, Fadle N, Pfreundschuh M, Sahin U. Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease. J Biol Chem 1997; 272(10): 6416-22.", "Heusschen R, Griffioen AW, Thijssen VL. Galectin-9 in tumor biology: A jack of m\u00faltiple trades. Biochim Biophys Acta 2013; 1836(1): 177-85.", "John S and Mishra R. Galectin-9: From cell biology to complex disease dynamics. J Biosci. 2016; 41(3): 507-34.", "Fujita K, Iwama H, Gura K, Tadokoro T, Samukawa E, Sakamoto T, et al. C\u00e1ncer Therapy Due to Apoptosis: Galectin-9. Int J Mol Sci 2017; 18(1): 74.", "Earl LA, Bi S, Baum LG. Galectin multimerization and lattice formation are regulated by linker regi\u00f3n structure. Glycobiology 2011; 21(1):6-12.", "Nishi N, Itoh A, Fujiyama A, Yoshida N, Araya S, Hirashima M. et al. Development of highly stable galectins: Truncation of the linker peptide confers protease-resistance on tandem-repeat type galectins. FEBS Lett 2005; 579(10):2058- 64.", "Hirashima M, Kashio Y, Nishi N, Yamauchi A, Imaizumi T, Kageshita T, et al. Galectin-9 in physiological and pathological conditions. Glycoconj J 2002; 19(7-9): 593-600.", "Zhu C, Anderson AC, Schubart A, Xiong H, Imit\u00f3la J, Khoury SJ, et al. The Tim-3 ligand galectin-9 [45] \tnegatively regulates T helper type 1 immunity. Nat Immunol 2005; 6(12): 1245-52.", "Zhang ZY, Dong JH, Chen YW, Wang XQ, Li CH, Wang J, et al. Galectin-9 acts as a prognostic factor with antimetastatic potential in hepatocellular carcinoma. As\u00edan Pac J C\u00e1ncer Prev 2012; 13(6):2503-9.", "Laderach DJ, Gentilini LD, Giribaldi L, Delgado VC, Nugnes L, Croci DO, et al. A unique galectin signature in human prostate c\u00e1ncer progression suggests galectin-1 as a key target for treatment of advanced disease. C\u00e1ncer Res 2013; 73(l):86-96.", "Mayoral MA, Mayoral C, Meneses A, Villalvazo L, Guzman A, Espinosa B, et al. Identification of galectin-3 and mucin-type O-glycans in breast c\u00e1ncer and its met\u00e1stasis to brain. C\u00e1ncer Investig 2008; 26(6): 615-23.", "Cada Z, Smetana K, Lacina L, Plz\u00e1kov\u00e1 Z, Stork J., Kaltner H, et al. Immunohistochemical fingerprinting of the network of seven adhesion/growth-regulatory lectins in human skin and detection of distinct tumour-associated alterations. Folia Biol (Praha) 2009; 55(4): 145\u00ad52.", "Kageshita T, Kashio Y, Yamauchi A, Seki M, Abedin MJ, Nishi N, et al. Possible role of galectin-9 \u00a1n cell aggregation and apoptosis of human melanoma cell Unes and its clinical significance. Int J C\u00e1ncer 2002; 99(6): 809-16.", "Labrie M, Oliveira Fernandes De Araujo L, Communal L, Mes-Masson AM, St-Pierre Y. Tissue and plasma levels of galectins in patients with high grade serous ovar\u00edan carcinoma as new predictive biomarkers. Sel Rep 2017; 7(1): 13244.", "Chan SW, Kallarakkal TG, Abraham MT. Changed expression of E-cadherin and galectin- 9 in oral squamous cell carcinomas but lack of potential as prognostic markers. As\u00edan Pac J C\u00e1ncer Prev 2014; 15(5):2145-52.", "Terris B, Blaveri E, Crnogorac-Jurcevic T, Jones M, Missiaglia E, Ruszniewski P, et al. Characterization of gene expression profiles in intraductal papillary-mucinous tumors of the p\u00e1ncreas. Am J Pathol 2002; 160(5): 1745-54.", "Yang J, Zhu L, Cai Y, Suo J, Jin J. Role of downregulation of galectin-9 in the tumorigenesis of gastric c\u00e1ncer. Int J Oncol 2014; 45(3): 1313-20.", "Jiang J, Jin MS, Kong F, Cao D, Ma HX, Jia Z, et al. Decreased galectin-9 and increased Tim-3 expression are related to poor prognosis in gastric c\u00e1ncer. PLoS ONE 2013; 8(12): e81799.", "Liang M, lleno M, Oomizu S, Arikawa T, Shinonaga R, Zhang S, et al. Galectin-9 expression links to malignant potential of cervical squamous cell carcinoma. J C\u00e1ncer Res Clin Oncol 2008; 134(8): 899-907.", "Punt S, Thijssen VL, Vrolijk J, de Kroon CD, Gorter A, et al. Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical C\u00e1ncer. PLoS ONE 2015; 10(6): in Squamous Cervical C\u00e1ncer. PLoS ONE 2015; 10(6): e0129119.", "Takano J, Morishita A, Fujihara S, Iwama H, Kokado F, Fujikawa K, et al. Galectin-9 suppresses the proliferation of gastric c\u00e1ncer cells in vitro. Oncol Rep 2016; 35(2):851-60.", "Akashi E, Fujihara S, Morishita A, Tadokoro T, Chiyo T, Fujikawa K, Kobara H, Mor\u00ed H, Iwama H, Okano K, Suzuki Y, Niki T, Hirashima M, Masaki T. Effects of galectin-9 on apoptosis, cell eyele and autophagy in human esophageal adenocarcinoma cells. Oncol Rep. 2017; 38(1): 506-514.", "Tadokoro T, Morishita A, Fujihara S, Iwama H, Niki T, Fujita K, et al. Galectin-9: An anticancer molecule for gallbladder carcinoma. Int J Oncol 2016; 48(3): 1165-74.", "Kuroda J, Yamamoto M, Nagoshi H, Kobayashi T, Sasaki N, Shimura Y, et al. Targeting activating transcription factor 3 by galectin-9 induces apoptosis and overcomes various types of treatment resistance in chronic myelogenous leukemia. Mol C\u00e1ncer Res 2010; 8(7):994-1001", "Kobayashi T, Kuroda J, Ashihara E, Oomizu S, Terui Y, Taniyama A, et al. Galectin-9 exhibits antimyeloma activity through JNK and p38 MAP kinase pathways. Leukemia 2010; 24(4): 843\u00ad50.", "Kikushige Y, Miyamoto T, Yuda J, Jabbarzadeh-Tabrizi S, Shima T, Takayanagi S-1, et al. ATTM-3/Gal 9 autocrine stimulatory loop drives self-renewal of human myeloid leukemia stem cells and leukemic progression. Cell Stem Cell 2015; 3;17(3):341-52.", "Wagner EF, Nebreda AR. Signal integration by JNK and p38 MAPK pathways in c\u00e1ncer development. Nat Rev C\u00e1ncer 2009; 9(8): 537\u00ad49.", "Dabrowska C, L\u00a1 M, Fan Y. Apoptotic Caspases in Promoting C\u00e1ncer: Implications from Their Roles in Development and Tissue Homeostasis. Adv Exp Med Biol. 2016; 930:89- 112.", "Irle A, Yamauchi A, Kontani K, Kihara M, Liu D, Shirato Y, et al. Galectin-9 as a prognostic factor with antimetastatic potential in breast c\u00e1ncer. Clin C\u00e1ncer Res 2005; 11(8):2962-8.", "Kasamatsu A, Uzawa K, Nakashima D, Koike H, Shiiba M, Bukawa H, et al. Galectin-9 as a regulator of cellular adhesi\u00f3n in human oral squamous cell carcinoma cell lines. Int J Mol Med 2005;16(2): 269-73.", "Nobumoto A, Nagahara K, Oomizu S, Katoh S, Nishi N, Takeshita K, et al. Galectin-9 suppresses tumor met\u00e1stasis by blocking adhesi\u00f3n to endothelium and extracellular matrices. Glycobiology 2008; 18(9): 735-44.", "Fujita K, Iwama H, Sakamoto T, Okura R, Kobayashi K, Takano J, et al. Galectin-9 suppresses the growth of hepatocellular carcinoma via apoptosis in vitro and in vivo. Int J Oncol 2015; 46(6):2419-30.", "Kobayashi K, Morishita A, Iwama H, Fujita K, Okura R, Fujihara S, et al. Galectin-9 suppresses cholangiocarcinoma cell proliferation by inducing apoptosis but not cell cycle arrest. Oncol Rep 2015; 34(4): 1761-70.", "Tadokoro T, Fujihara S, Chiyo T, Oura K, Samukawa E, Yamana Y, et al. Induction of apoptosis by Galectin-9 in liver metastatic c\u00e1ncer cells: In vitro study. Int J Oncol 2017;51(2):607-614.", "Seki M, Oomizu S, Sakata KM, Sakata A, Arikawa T, Watanabe K, et al. Galectin-9 suppresses the generation of Thl7, promotes the induction of regulatoryT cells, and regulates experimental autoimmune arthritis. Clin Immunol 2008;127(l):78-88.", "Mengshol JA, Golden-Mason L, Arikawa T, Smith M, Niki T, McWilliams R, et al. A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection. PLoS ONE 2010;5: e9504.", "Kurose Y, Wada J, Kanzaki M, Teshigawara S, Nakatsuka A, Murakami K, et al. Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease. BMC Nephrol 2013; 22; 14:23.", "Brubel R, Bokor A, Pohl A, Schilli GK, Szereday L, Bacher-Szamuel R, et al. Serum galectin-9 as a noninvasive biomarker for the detection of endometriosis and pelvic pain or infertility-related gynecologic disorders. F\u00e9rtil Steril. 2017;108(6):1016-1025.e2.", "Liu KT, Liu YH, Chen YH, Lin CY, Huang CH, Yen MC, et al. Serum Galectin-9 and Galectin-3- Binding Protein in Acute Dengue Virus Infection. Int J Mol Sci 2016; 27; 17(6)."]}

RESUMEN Galectina-9 pertenece a la familia de las galectinas que tienen la capacidad de unir β-galactósidos presentes en glicoproteínas y glicolípidos, a través de sus dos dominios de reconocimiento a carbohidratos. La galectina-9 puede ejercer sus funciones a nivel extracelular e intracelular. A nivel extracelular participa mediando la interacción entre proteínas de membrana de superficie celular con componentes de la matriz extracelular. La proteína se expresa en distintos tipos celulares como en hígado, intestino delgado, timo, riñón, bazo, pulmón, músculo esquelético, músculo cardiaco, cerebro, placenta, páncreas, próstata y colon. En diversos tipos de cáncer, como carcinoma hepatocelular, cáncer de próstata, de mama, cervicouterino, de piel, oral, de páncreas, de ovario, gástrico y hematológicos la expresión del ARNm de galectina-9 y de la proteína está alterada. En algunos casos, dichos cambios de expresión están asociados a grados de la enfermedad, supervivencia y respuesta a tratamiento. El estudio de la función de galectina-9 a través de modelos in vitro e in vivo han permitido conocer que la proteína participa en la apoptosis de células cancerosas, promoción de la adhesión celular e inhibición de la metástasis sugiriendo, en la mayoría de los casos, un efecto protector contra el cáncer. ABSTRACT Galectin-9 belongs to the galectins family that have the ability to bind β-galactosides present in glycoproteins and glycolipids, through their carbohydrate recognition domains. Galectin-9 can perform its functions at the extracellular and intracellular level. At the extracellular level, it participates by mediating the interaction between cell surface membrane proteins with components of the extracellular matrix. The protein is expressed in different cell types such as liver, small intestine, thymus, kidney, spleen, lung, skeletal muscle, heart muscle, brain, placenta, pancreas, prostate and colon. In several types of cancer, such as hepatocellular carcinoma, prostate, breast, cervical, skin, oral, pancreas, ovarian, gastric and hematological cancers, the expression of galectin-9 mRNA and protein is altered. In some cases, these changes in expression are associated with degrees of disease, survival, and response to treatment. The study of the function of galectin-9 through in vitro and in vivo models have revealed that the protein participates in apoptosis of cancer cells, promotion of cell adhesion and inhibition of metastasis, suggesting, in most cases, a protective effect against cancer.