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Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion

Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This...

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Autores principales: Guerrero, Pedro Enrique, Miró, Laura, Wong, Bin S., Massaguer, Anna, Martínez-Bosch, Neus, de Llorens, Rafael, Navarro, Pilar, Konstantopoulos, Konstantinos, Llop, Esther, Peracaula, Rosa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503936/
https://www.ncbi.nlm.nih.gov/pubmed/32872308
http://dx.doi.org/10.3390/ijms21176239
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author Guerrero, Pedro Enrique
Miró, Laura
Wong, Bin S.
Massaguer, Anna
Martínez-Bosch, Neus
de Llorens, Rafael
Navarro, Pilar
Konstantopoulos, Konstantinos
Llop, Esther
Peracaula, Rosa
author_facet Guerrero, Pedro Enrique
Miró, Laura
Wong, Bin S.
Massaguer, Anna
Martínez-Bosch, Neus
de Llorens, Rafael
Navarro, Pilar
Konstantopoulos, Konstantinos
Llop, Esther
Peracaula, Rosa
author_sort Guerrero, Pedro Enrique
collection PubMed
description Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the α2,3-STs and fucosyltransferases involved in the biosynthesis of sLe antigens, using a panel of human PDA cells showed differences in the levels of sialylated determinants and α2,3-STs expression, reflecting their phenotypic heterogeneity. Knockdown of ST3GAL3 and ST3GAL4 in BxPC-3 and Capan-1 cells, which expressed moderate to high levels of sLe antigens and α2,3-STs, led to a significant reduction in sLe(x) and in most cases in sLe(a), with slight increases in the α2,6-sialic acid content. Moreover, ST3GAL3 and ST3GAL4 downregulation resulted in a significant decrease in cell migration and invasion. Binding and rolling to E-selectin, which represent key steps in metastasis, were also markedly impaired in the α2,3-STs knockdown cells. Our results indicate that inhibition of ST3GAL3 and ST3GAL4 may be a novel strategy to block PDA metastasis, which is one of the reasons for its dismal prognosis.
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spelling pubmed-75039362020-09-27 Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion Guerrero, Pedro Enrique Miró, Laura Wong, Bin S. Massaguer, Anna Martínez-Bosch, Neus de Llorens, Rafael Navarro, Pilar Konstantopoulos, Konstantinos Llop, Esther Peracaula, Rosa Int J Mol Sci Article Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). α2,3-Sialyltransferases (α2,3-STs) ST3GAL3 and ST3GAL4 are overexpressed in PDA tissues and are responsible for increased biosynthesis of sialyl-Lewis (sLe) antigens, which play an important role in metastasis. This study addresses the effect of α2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the α2,3-STs and fucosyltransferases involved in the biosynthesis of sLe antigens, using a panel of human PDA cells showed differences in the levels of sialylated determinants and α2,3-STs expression, reflecting their phenotypic heterogeneity. Knockdown of ST3GAL3 and ST3GAL4 in BxPC-3 and Capan-1 cells, which expressed moderate to high levels of sLe antigens and α2,3-STs, led to a significant reduction in sLe(x) and in most cases in sLe(a), with slight increases in the α2,6-sialic acid content. Moreover, ST3GAL3 and ST3GAL4 downregulation resulted in a significant decrease in cell migration and invasion. Binding and rolling to E-selectin, which represent key steps in metastasis, were also markedly impaired in the α2,3-STs knockdown cells. Our results indicate that inhibition of ST3GAL3 and ST3GAL4 may be a novel strategy to block PDA metastasis, which is one of the reasons for its dismal prognosis. MDPI 2020-08-28 /pmc/articles/PMC7503936/ /pubmed/32872308 http://dx.doi.org/10.3390/ijms21176239 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Guerrero, Pedro Enrique
Miró, Laura
Wong, Bin S.
Massaguer, Anna
Martínez-Bosch, Neus
de Llorens, Rafael
Navarro, Pilar
Konstantopoulos, Konstantinos
Llop, Esther
Peracaula, Rosa
Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title_full Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title_fullStr Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title_full_unstemmed Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title_short Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
title_sort knockdown of α2,3-sialyltransferases impairs pancreatic cancer cell migration, invasion and e-selectin-dependent adhesion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503936/
https://www.ncbi.nlm.nih.gov/pubmed/32872308
http://dx.doi.org/10.3390/ijms21176239
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