1. Knockdown of α2,3-Sialyltransferases Impairs Pancreatic Cancer Cell Migration, Invasion and E-selectin-Dependent Adhesion
- Author
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Esther Llop, Pilar Navarro, Pedro Enrique Guerrero, Anna Massaguer, Laura Miró, Bin Sheng Wong, Neus Martínez-Bosch, Rosa Peracaula, Rafael de Llorens, Konstantinos Konstantopoulos, Ministerio de Economía y Competitividad (España), Universidad de Girona, Generalitat de Catalunya, Instituto de Salud Carlos III, European Commission, Guerrero, Pedro E., Miró, Laura, Navarro, Pilar, Llop, Esther, Peracaula, Rosa, Ministerio de Economía y Competitividad (Espanya), Guerrero, Pedro E. [0000-0003-2612-9235], Miró, Laura [0000-0002-7111-1811], Navarro, Pilar [0000-0003-4314-4584], Llop, Esther [0000-0003-0929-4888], and Peracaula, Rosa [0000-0003-3513-524X]
- Subjects
0301 basic medicine ,cell migration ,Cell ,α2,3-sialyltransferases ,Metastasis ,lcsh:Chemistry ,Pancreatic ductal adenocarcinoma ,0302 clinical medicine ,Cell Movement ,RNA, Small Interfering ,lcsh:QH301-705.5 ,Spectroscopy ,Gene knockdown ,E-selectin ,Cell migration ,General Medicine ,Fucosyltransferases ,humanities ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,Sialyl-Lewis antigens ,medicine.anatomical_structure ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,congenital, hereditary, and neonatal diseases and abnormalities ,education ,pancreatic ductal adenocarcinoma ,Biology ,Gene Expression Regulation, Enzymologic ,Catalysis ,Article ,Inorganic Chemistry ,03 medical and health sciences ,Lewis Blood Group Antigens ,Downregulation and upregulation ,Antigen ,Cell Line, Tumor ,health services administration ,medicine ,Humans ,Physical and Theoretical Chemistry ,Pancreas -- Cancer ,Molecular Biology ,Pàncrees -- Càncer ,Organic Chemistry ,medicine.disease ,Sialyltransferases ,Pancreatic Neoplasms ,carbohydrates (lipids) ,sialyl-Lewis antigens ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,ST3GAL3 ,Cancer research ,biology.protein - Abstract
Aberrant sialylation is frequently found in pancreatic ductal adenocarcinoma (PDA). &alpha, 2,3-Sialyltransferases (&alpha, 2,3-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 &alpha, 2,3-STs knockdown on the migratory and invasive phenotype of PDA cells, and on E-selectin-dependent adhesion. Characterization of the cell sialome, the &alpha, 2,3-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 &alpha, 2,3-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 &alpha, 2,3-STs, led to a significant reduction in sLex and in most cases in sLea, with slight increases in the &alpha, 2,6-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 &alpha, 2,3-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.
- Published
- 2020
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