Artículo

Ferragut, F.; Cagnoni, A.J.; Colombo, L.L.; Sánchez Terrero, C.; Wolfenstein-Todel, C.; Troncoso, M.F.; Vanzulli, S.I.; Rabinovich, G.A.; Mariño, K.V.; Elola, M.T. "Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth" (2019) Biochimica et Biophysica Acta - Molecular Cell Research
El editor solo permite decargar el artículo en su versión post-print desde el repositorio. Por favor, si usted posee dicha versión, enviela a
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Galectin-8 (Gal-8), a ‘tandem-repeat’-type galectin, has been described as a modulator of cellular functions including adhesion, spreading, growth arrest, apoptosis, pathogen recognition, autophagy, and immunomodulation. We have previously shown that activated leukocyte cell adhesion molecule (ALCAM), also known as CD166, serves as a receptor for endogenous Gal-8. ALCAM is a member of the immunoglobulin superfamily involved in cell-cell adhesion through homophilic (ALCAM-ALCAM) and heterophilic (i.e. ALCAM-CD6) interactions in different tissues. Here we investigated the physiologic relevance of ALCAM-Gal-8 association and glycosylation-dependent mechanisms governing these interactions. We found that silencing of ALCAM in MDA-MB-231 triple negative breast cancer cells decreases cell adhesion and migration onto Gal-8-coated surfaces in a glycan-dependent fashion. Remarkably, either Gal-8 or ALCAM silencing also disrupted cell-cell adhesion, and led to reduced tumor growth in a murine model of triple negative breast cancer. Moreover, structural characterization of endogenous ALCAM N-glycosylation showed abundant permissive structures for Gal-8 binding. Importantly, we also found that cell sialylation controls Gal-8-mediated cell adhesion. Altogether, these findings demonstrate a central role of either ALCAM or Gal-8 (or both) in controlling triple negative breast cancer. © 2019 Elsevier B.V.

Registro:

Documento: Artículo
Título:Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
Autor:Ferragut, F.; Cagnoni, A.J.; Colombo, L.L.; Sánchez Terrero, C.; Wolfenstein-Todel, C.; Troncoso, M.F.; Vanzulli, S.I.; Rabinovich, G.A.; Mariño, K.V.; Elola, M.T.
Filiación:Instituto de Química y Fisicoquímica Biológicas Prof. Dr. Alejandro Paladini (CONICET-UBA), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina
Laboratorio de Glicómica Funcional y Molecular, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
Área de Investigación, Instituto de Oncología Ángel H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina
Centro Oncológico de Medicina Nuclear, Comisión Nacional de Energía Atómica-Hospital Oncológico Ángel H. Roffo, Universidad de Buenos Aires, Buenos Aires, Argentina
Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional de Medicina, Buenos Aires, Argentina
Laboratorio de Inmunopatología, Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:ALCAM (CD166); Cell adhesion and migration; Galectin-8; N-glycosylation; Sialylation; Triple negative breast cancer; Tumor growth
Año:2019
DOI: http://dx.doi.org/10.1016/j.bbamcr.2019.03.010
Título revista:Biochimica et Biophysica Acta - Molecular Cell Research
Título revista abreviado:Biochim. Biophys. Acta Mol. Cell Res.
ISSN:01674889
CODEN:BAMRD
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_01674889_v_n_p_Ferragut

Referencias:

  • Cerliani, J.P., Blidner, A.G., Toscano, M.A., Croci, D.O., Rabinovich, G.A., Translating the ‘sugar code’ into immune and vascular signaling programs (2017) Trends Biochem. Sci., 42, pp. 255-273
  • Elola, M.T., Ferragut, F., Méndez-Huergo, S.P., Croci, D.O., Bracalente, C., Rabinovich, G.A., Galectins: multitask signaling molecules linking fibroblast, endothelial and immune cell programs in the tumor microenvironment (2018) Cell. Immunol., 333, pp. 34-45
  • Bidon, N., Brichory, F., Hanash, S., Bourguet, P., Dazord, L., Le Pennec, J.P., Two messenger RNAs and five isoforms for Po66-CBP, a galectin-8 homolog in a human lung carcinoma cell line (2001) Gene, 274, pp. 253-262
  • Zick, Y., Eisenstein, M., Goren, R.A., Hadari, Y.R., Levy, Y., Ronen, D., Role of galectin-8 as a modulator of cell adhesion and cell growth (2004) Glycoconj. J., 19, pp. 517-526
  • Hadari, Y.R., Arbel-Goren, R., Levy, Y., Amsterdam, A., Alon, R., Zakut, R., Zick, Y., Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis (2000) J. Cell Sci., 113, pp. 2385-2397
  • Levy, Y., Arbel-Goren, R., Hadari, Y.R., Eshhar, S., Ronen, D., Elhanany, E., Geiger, B., Zick, Y., Galectin-8 functions as a matricellular modulator of cell adhesion (2001) J. Biol. Chem., 276, pp. 31285-31295
  • Levy, Y., Ronen, D., Bershadsky, A.D., Zick, Y., Sustained induction of ERK, protein kinase B, and p70 S6 kinase regulates cell spreading and formation of F-actin microspikes upon ligation of integrins by galectin-8, a mammalian lectin (2003) J. Biol. Chem., 278, pp. 14533-14542
  • Arbel-Goren, R., Levy, Y., Ronen, D., Zick, Y., Cyclin-dependent kinase inhibitors and JNK act as molecular switches, regulating the choice between growth arrest and apoptosis induced by galectin-8 (2005) J. Biol. Chem., 280, pp. 19105-19114
  • Stowell, S.R., Arthur, C.M., Dias-Baruffi, M., Rodrigues, L.C., Gourdine, J.P., Heimburg-Molinaro, J., Ju, T., Cummings, R.D., Innate immune lectins kill bacteria expressing blood group antigen (2010) Nat. Med., 16, pp. 295-301
  • Thurston, T.L., Wandel, M.P., von Muhlinen, N., Foeglein, A., Randow, F., Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion (2012) Nature, 482, pp. 414-418
  • Falcon, B., Noad, J., McMahon, H., Randow, F., Goedert, M., Galectin-8-mediated selective autophagy protects against seeded tau aggregation (2018) J. Biol. Chem., 293, pp. 2438-2451
  • Sampson, J.F., Suryawanshi, A., Chen, W.S., Rabinovich, G.A., Panjwani, N., Galectin-8 promotes regulatory T-cell differentiation by modulating IL-2 and TGFbeta signaling (2016) Immunol. Cell Biol., 94, pp. 213-219
  • Danguy, A., Rorive, S., Decaestecker, C., Bronckart, Y., Kaltner, H., Hadari, Y.R., Goren, R., Kiss, R., Immunohistochemical profile of galectin-8 expression in benign and malignant tumors of epithelial, mesenchymatous and adipous origins, and of the nervous system (2001) Histol. Histopathol., 16, pp. 861-868
  • Lahm, H., Andre, S., Hoeflich, A., Fischer, J.R., Sordat, B., Kaltner, H., Wolf, E., Gabius, H.J., Comprehensive galectin fingerprinting in a panel of 61 human tumor cell lines by RT-PCR and its implications for diagnostic and therapeutic procedures (2001) J. Cancer Res. Clin. Oncol., 127, pp. 375-386
  • Bidon-Wagner, N., Le Pennec, J.P., Human galectin-8 isoforms and cancer (2004) Glycoconj. J., 19, pp. 557-563
  • Elola, M.T., Ferragut, F., Cardenas Delgado, V.M., Nugnes, L.G., Gentilini, L., Laderach, D., Troncoso, M.F., Rabinovich, G.A., Expression, localization and function of galectin-8, a tandem-repeat lectin (2014) in human tumors, Histol. Histopathol., 29, pp. 1093-1105
  • Vinik, Y., Shatz-Azoulay, H., Zick, Y., Molecular mechanisms underlying the role of galectin-8 as a regulator of cancer growth and metastasis (2018) Trends Glycosci. Glyc., 30, pp. SE119-SE128
  • Lu, H., Knutson, K.L., Gad, E., Disis, M.L., The tumor antigen repertoire identified in tumor-bearing neu transgenic mice predicts human tumor antigens (2006) Cancer Res., 66, pp. 9754-9761
  • Barrow, H., Guo, X., Wandall, H.H., Pedersen, J.W., Fu, B., Zhao, Q., Chen, C., Yu, L.G., Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium (2011) Clin. Cancer Res., 17, pp. 7035-7046
  • Fernández, M.M., Ferragut, F., Cardenas Delgado, V.M., Bracalente, C., Bravo, A.I., Cagnoni, A.J., Nunez, M., Elola, M.T., Glycosylation-dependent binding of galectin-8 to activated leukocyte cell adhesion molecule (ALCAM/CD166) promotes its surface segregation on breast cancer cells (2016) Biochim. Biophys. Acta, 1860, pp. 2255-2268
  • Oyanadel, C., Holmes, C., Pardo, E., Retamal, C., Shaughnessy, R., Smith, P., Cortes, P., Gonzalez, A., Galectin-8 induces partial epithelial-mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin-Darby canine kidney cells (2018) Mol. Biol. Cell, 29, pp. 557-574
  • Cárcamo, C., Pardo, E., Oyanadel, C., Bravo-Zehnder, M., Bull, P., Cáceres, M., Martínez, J., Soza, A., Galectin-8 binds specific beta1 integrins and induces polarized spreading highlighted by asymmetric lamellipodia in Jurkat T cells (2006) Exp. Cell Res., 312, pp. 374-386
  • Levy, Y., Auslender, S., Eisenstein, M., Vidavski, R.R., Ronen, D., Bershadsky, A.D., Zick, Y., It depends on the hinge: a structure-functional analysis of galectin-8, a tandem-repeat type lectin (2006) Glycobiology, 16, pp. 463-476
  • Diskin, S., Chen, W.S., Cao, Z., Gyawali, S., Gong, H., Soza, A., Gonzalez, A., Panjwani, N., Galectin-8 promotes cytoskeletal rearrangement in trabecular meshwork cells through activation of Rho signaling (2012) PLoS One, 7
  • Camby, I., Belot, N., Rorive, S., Lefranc, F., Maurage, C.A., Lahm, H., Kaltner, H., Kiss, R., Galectins are differentially expressed in supratentorial pilocytic astrocytomas, astrocytomas, anaplastic astrocytomas and glioblastomas, and significantly modulate tumor astrocyte migration (2001) Brain Pathol., 11, pp. 12-26
  • Metz, C., Doger, R., Riquelme, E., Cortes, P., Holmes, C., Shaughnessy, R., Oyanadel, C., Soza, A., Galectin-8 promotes migration and proliferation and prevents apoptosis in U87 glioblastoma cells (2016) Biol. Res., 49, p. 33
  • Reticker-Flynn, N.E., Malta, D.F., Winslow, M.M., Lamar, J.M., Xu, M.J., Underhill, G.H., Hynes, R.O., Bhatia, S.N., A combinatorial extracellular matrix platform identifies cell-extracellular matrix interactions that correlate with metastasis (2012) Nat. Commun., 3, p. 1122
  • Cueni, L.N., Detmar, M., Galectin-8 interacts with podoplanin and modulates lymphatic endothelial cell functions (2009) Exp. Cell Res., 315, pp. 1715-1723
  • Delgado, V.M., Nugnes, L.G., Colombo, L.L., Troncoso, M.F., Fernandez, M.M., Malchiodi, E.L., Frahm, I., Elola, M.T., Modulation of endothelial cell migration and angiogenesis: a novel function for the “tandem-repeat” lectin galectin-8 (2011) FASEB J., 25, pp. 242-254
  • Friedel, M., Andre, S., Goldschmidt, H., Gabius, H.J., Schwartz-Albiez, R., Galectin-8 enhances adhesion of multiple myeloma cells to vascular endothelium and is an adverse prognostic factor (2016) Glycobiology, 26, pp. 1048-1058
  • Etulain, J., Negrotto, S., Tribulatti, M.V., Croci, D.O., Carabelli, J., Campetella, O., Rabinovich, G.A., Schattner, M., Control of angiogenesis by galectins involves the release of platelet-derived proangiogenic factors (2014) PLoS One, 9, p. e96402
  • Vinik, Y., Shatz-Azoulay, H., Vivanti, A., Hever, N., Levy, Y., Karmona, R., Brumfeld, V., Zick, Y., The mammalian lectin galectin-8 induces RANKL expression, osteoclastogenesis, and bone mass reduction in mice (2015) Elife, 4
  • Vinik, Y., Shatz-Azoulay, H., Hiram-Bab, S., Kandel, L., Gabet, Y., Rivkin, G., Zick, Y., Ablation of the mammalian lectin galectin-8 induces bone defects in mice (2018) FASEB J., 32, pp. 2366-2380
  • Swart, G.W., Lunter, P.C., Kilsdonk, J.W., Kempen, L.C., Activated leukocyte cell adhesion molecule (ALCAM/CD166): signaling at the divide of melanoma cell clustering and cell migration? (2005) Cancer Metastasis Rev., 24, pp. 223-236
  • Hansen, A.G., Swart, G.W., Zijlstra, A., ALCAM: basis sequence: mouse (2011) AFCS Nat. Mol. Pages, 2011
  • Hebron, K.E., Li, E.Y., Arnold Egloff, S.A., von Lersner, A.K., Taylor, C., Houkes, J., Flaherty, D.K., Zijlstra, A., Alternative splicing of ALCAM enables tunable regulation of cell-cell adhesion through differential proteolysis (2018) Sci. Rep., 8, p. 3208
  • Hansen, A.G., Arnold, S.A., Jiang, M., Palmer, T.D., Ketova, T., Merkel, A., Pickup, M., Zijlstra, A., ALCAM/CD166 is a TGF-beta-responsive marker and functional regulator of prostate cancer metastasis to bone (2014) Cancer Res., 74, pp. 1404-1415
  • Fujiwara, K., Ohuchida, K., Sada, M., Horioka, K., Ulrich, C.D., Shindo, K., Ohtsuka, T., Tanaka, M., CD166/ALCAM expression is characteristic of tumorigenicity and invasive and migratory activities of pancreatic cancer cells (2014) PLoS One, 9
  • Ma, L., Wang, J., Lin, J., Pan, Q., Yu, Y., Sun, F., Cluster of differentiation 166 (CD166) regulated by phosphatidylinositide 3-Kinase (PI3K)/AKT signaling to exert its anti-apoptotic role via yes-associated protein (YAP) in liver cancer (2014) J. Biol. Chem., 289, pp. 6921-6933
  • Yu, W., Wang, J., Ma, L., Tang, X., Qiao, Y., Pan, Q., Yu, Y., Sun, F., CD166 plays a pro-carcinogenic role in liver cancer cells via inhibition of FOXO proteins through AKT (2014) Oncol. Rep., 32, pp. 677-683
  • Tang, X., Chen, X., Xu, Y., Qiao, Y., Zhang, X., Wang, Y., Guan, Y., Wang, J., CD166 positively regulates MCAM via inhibition to ubiquitin E3 ligases Smurf1 and betaTrCP through PI3K/AKT and c-Raf/MEK/ERK signaling in Bel-7402 hepatocellular carcinoma cells (2015) Cell. Signal., 27, pp. 1694-1702
  • Devis, L., Moiola, C.P., Masia, N., Martinez-Garcia, E., Santacana, M., Stirbat, T.V., Brochard-Wyart, F., Colas, E., Activated leukocyte cell adhesion molecule (ALCAM) is a marker of recurrence and promotes cell migration, invasion, and metastasis in early-stage endometrioid endometrial cancer (2017) J. Pathol., 241, pp. 475-487
  • Hirabayashi, J., Hashidate, T., Arata, Y., Nishi, N., Nakamura, T., Hirashima, M., Urashima, T., Kasai, K., Oligosaccharide specificity of galectins: a search by frontal affinity chromatography (2002) Biochim. Biophys. Acta, 1572, pp. 232-254
  • Ideo, H., Seko, A., Ishizuka, I., Yamashita, K., The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity (2003) Glycobiology, 13, pp. 713-723
  • Carlsson, S., Oberg, C.T., Carlsson, M.C., Sundin, A., Nilsson, U.J., Smith, D., Cummings, R.D., Leffler, H., Affinity of galectin-8 and its carbohydrate recognition domains for ligands in solution and at the cell surface (2007) Glycobiology, 17, pp. 663-676
  • Ideo, H., Matsuzaka, T., Nonaka, T., Seko, A., Yamashita, K., Galectin-8-N-domain recognition mechanism for sialylated and sulfated glycans (2011) J. Biol. Chem., 286, pp. 11346-11355
  • Yoshida, H., Yamashita, S., Teraoka, M., Itoh, A., Nakakita, S., Nishi, N., Kamitori, S., X-ray structure of a protease-resistant mutant form of human galectin-8 with two carbohydrate recognition domains (2012) FEBS J., 279, pp. 3937-3951
  • Jensen, P.H., Karlsson, N.G., Kolarich, D., Packer, N.H., Structural analysis of N- and O-glycans released from glycoproteins (2012) Nat. Protoc., 7, pp. 1299-1310
  • Royle, L., Dwek, R.A., Rudd, P.M., Determining the structure of oligosaccharides N- and O-linked to glycoproteins (2006) Curr. Protoc. Protein Sci, pp. 1-45
  • Saldova, R., Asadi Shehni, A., Haakensen, V.D., Steinfeld, I., Hilliard, M., Kifer, I., Helland, A., Rudd, P.M., Association of N-glycosylation with breast carcinoma and systemic features using high-resolution quantitative UPLC (2014) J. Proteome Res., 13, pp. 2314-2327
  • Mariño, K., Bones, J., Kattla, J.J., Rudd, P.M., A systematic approach to protein glycosylation analysis: a path through the maze (2010) Nat. Chem. Biol., 6, pp. 713-723
  • Elola, M.T., Wolfenstein-Todel, C., Troncoso, M.F., Vasta, G.R., Rabinovich, G.A., Galectins: matricellular glycan-binding proteins linking cell adhesion, migration, and survival (2007) Cell. Mol. Life Sci., 64, pp. 1679-1700
  • Hein, S., Muller, V., Kohler, N., Wikman, H., Krenkel, S., Streichert, T., Schweizer, M., Milde-Langosch, K., Biologic role of activated leukocyte cell adhesion molecule overexpression in breast cancer cell lines and clinical tumor tissue (2011) Breast Cancer Res. Treat., 129, pp. 347-360
  • Gentilini, L.D., Jaworski, F.M., Tiraboschi, C., Perez, I.G., Kotler, M.L., Chauchereau, A., Laderach, D.J., Compagno, D., Stable and high expression of Galectin-8 tightly controls metastatic progression of prostate cancer (2017) Oncotarget, 8, pp. 44654-44668
  • Jezierska, A., Matysiak, W., Motyl, T., ALCAM/CD166 protects breast cancer cells against apoptosis and autophagy (2006) Med. Sci. Monit., 12, pp. BR263-273
  • Ludwig, A.K., Michalak, M., Shilova, N., Andre, S., Kaltner, H., Bovin, N.V., Kopitz, J., Gabius, H.J., Studying the structural significance of galectin design by playing a modular puzzle: homodimer generation from human tandem-repeat-type (heterodimeric) galectin-8 by domain shuffling (2017) Molecules, 22, p. 1572
  • Patnaik, S.K., Potvin, B., Carlsson, S., Sturm, D., Leffler, H., Stanley, P., Complex N-glycans are the major ligands for galectin-1, -3, and -8 on Chinese hamster ovary cells (2006) Glycobiology, 16, pp. 305-317
  • Dam, T.K., Brewer, F.C., Maintenance of cell surface glycan density by lectin-glycan interactions: a homeostatic and innate immune regulatory mechanism (2010) Glycobiology, 20, pp. 1061-1064
  • Dennis, J.W., Brewer, C.F., Density-dependent lectin-glycan interactions as a paradigm for conditional regulation by posttranslational modifications (2013) Mol. Cell. Proteomics, 12, pp. 913-920
  • Yuan, Y., Wu, L., Shen, S., Wu, S., Burdick, M.M., Effect of alpha 2,6 sialylation on integrin-mediated adhesion of breast cancer cells to fibronectin and collagen IV (2016) Life Sci., 149, pp. 138-145
  • Lu, J., Isaji, T., Im, S., Fukuda, T., Kameyama, A., Gu, J., Expression of N-acetylglucosaminyltransferase III suppresses α2,3-sialylation, and its distinctive functions in cell migration are attributed to α2,6-sialylation levels (2016) J. Biol. Chem., 291, pp. 5708-5720
  • Isaji, T., Im, S., Kameyama, A., Wang, Y., Fukuda, T., Gu, J., A complex between phosphatidylinositol 4 kinase IIα and integrin α3β1 is required for N-glycan sialylation in cancer cells (2019) J. Biol. Chem.
  • Lebert, J.M., Lester, R., Powell, E., Seal, M., McCarthy, J., Advances in the systemic treatment of triple-negative breast cancer (2018) Curr. Oncol., 25, pp. S142-S150
  • Varki, A., Cummings, R.D., Aebi, M., Packer, N.H., Seeberger, P.H., Esko, J.D., Stanley, P., Kornfeld, S., Symbol nomenclature for graphical representations of glycans (2015) Glycobiology, 25, pp. 1323-1324

Citas:

---------- APA ----------
Ferragut, F., Cagnoni, A.J., Colombo, L.L., Sánchez Terrero, C., Wolfenstein-Todel, C., Troncoso, M.F., Vanzulli, S.I.,..., Elola, M.T. (2019) . Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth. Biochimica et Biophysica Acta - Molecular Cell Research.
http://dx.doi.org/10.1016/j.bbamcr.2019.03.010
---------- CHICAGO ----------
Ferragut, F., Cagnoni, A.J., Colombo, L.L., Sánchez Terrero, C., Wolfenstein-Todel, C., Troncoso, M.F., et al. "Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth" . Biochimica et Biophysica Acta - Molecular Cell Research (2019).
http://dx.doi.org/10.1016/j.bbamcr.2019.03.010
---------- MLA ----------
Ferragut, F., Cagnoni, A.J., Colombo, L.L., Sánchez Terrero, C., Wolfenstein-Todel, C., Troncoso, M.F., et al. "Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth" . Biochimica et Biophysica Acta - Molecular Cell Research, 2019.
http://dx.doi.org/10.1016/j.bbamcr.2019.03.010
---------- VANCOUVER ----------
Ferragut, F., Cagnoni, A.J., Colombo, L.L., Sánchez Terrero, C., Wolfenstein-Todel, C., Troncoso, M.F., et al. Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth. Biochim. Biophys. Acta Mol. Cell Res. 2019.
http://dx.doi.org/10.1016/j.bbamcr.2019.03.010