Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth

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...

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Autores principales: 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.
Formato: JOUR
Materias:
ALCAM (CD166)
Cell adhesion and migration
Galectin-8
N-glycosylation
Sialylation
Triple negative breast cancer
Tumor growth
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_01674889_v_n_p_Ferragut
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_01674889_v_n_p_Ferragut
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spelling todo:paper_01674889_v_n_p_Ferragut2023-10-03T15:04:53Z Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth 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. ALCAM (CD166) Cell adhesion and migration Galectin-8 N-glycosylation Sialylation Triple negative breast cancer Tumor growth 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_01674889_v_n_p_Ferragut
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic ALCAM (CD166)
Cell adhesion and migration
Galectin-8
N-glycosylation
Sialylation
Triple negative breast cancer
Tumor growth
spellingShingle ALCAM (CD166)
Cell adhesion and migration
Galectin-8
N-glycosylation
Sialylation
Triple negative breast cancer
Tumor growth
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
topic_facet ALCAM (CD166)
Cell adhesion and migration
Galectin-8
N-glycosylation
Sialylation
Triple negative breast cancer
Tumor growth
description 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.
format JOUR
author 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.
author_facet 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.
author_sort Ferragut, F.
title Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
title_short Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
title_full Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
title_fullStr Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
title_full_unstemmed Dual knockdown of Galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (ALCAM/CD166), synergistically delays in vivo breast cancer growth
title_sort dual knockdown of galectin-8 and its glycosylated ligand, the activated leukocyte cell adhesion molecule (alcam/cd166), synergistically delays in vivo breast cancer growth
url http://hdl.handle.net/20.500.12110/paper_01674889_v_n_p_Ferragut
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