Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells.
Sialyl-Lewis X (SLe(x)) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferase...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2013-01-01
|
Series: | PLoS ONE |
Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23799130/?tool=EBI |
id |
doaj-d472e14c9b00471c82434915f06d56fe |
---|---|
record_format |
Article |
spelling |
doaj-d472e14c9b00471c82434915f06d56fe2021-03-03T23:15:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0186e6673710.1371/journal.pone.0066737Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells.Catarina GomesHugo OsórioMarta Teixeira PintoDiana CamposMaria José OliveiraCelso A ReisSialyl-Lewis X (SLe(x)) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferases (STs). In this study we determined the capacity of ST3GAL3 and ST3GAL4 sialyltransferases to synthesize the SLe(x) antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLe(x) overexpression in cancer cell behavior both in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. The activation of tyrosine kinase receptors and their downstream molecular targets was also addressed. Our results showed that the expression of ST3GAL4 in MKN45 gastric cancer cells leads to the synthesis of SLe(x) antigens and to an increased invasive phenotype both in vitro and in the in vivo CAM model. Analysis of phosphorylation of tyrosine kinase receptors showed a specific increase in c-Met activation. The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and Src proteins and activation of Cdc42, Rac1 and RhoA GTPases. Inhibition of c-Met and Src activation abolished the observed increased cell invasive phenotype. In conclusion, the expression of ST3GAL4 leads to SLe(x) antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, in association with Src, FAK and Cdc42, Rac1 and RhoA GTPases activation.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23799130/?tool=EBI |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Catarina Gomes Hugo Osório Marta Teixeira Pinto Diana Campos Maria José Oliveira Celso A Reis |
spellingShingle |
Catarina Gomes Hugo Osório Marta Teixeira Pinto Diana Campos Maria José Oliveira Celso A Reis Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. PLoS ONE |
author_facet |
Catarina Gomes Hugo Osório Marta Teixeira Pinto Diana Campos Maria José Oliveira Celso A Reis |
author_sort |
Catarina Gomes |
title |
Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. |
title_short |
Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. |
title_full |
Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. |
title_fullStr |
Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. |
title_full_unstemmed |
Expression of ST3GAL4 leads to SLe(x) expression and induces c-Met activation and an invasive phenotype in gastric carcinoma cells. |
title_sort |
expression of st3gal4 leads to sle(x) expression and induces c-met activation and an invasive phenotype in gastric carcinoma cells. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Sialyl-Lewis X (SLe(x)) is a sialylated glycan antigen expressed on the cell surface during malignant cell transformation and is associated with cancer progression and poor prognosis. The increased expression of sialylated glycans is associated with alterations in the expression of sialyltransferases (STs). In this study we determined the capacity of ST3GAL3 and ST3GAL4 sialyltransferases to synthesize the SLe(x) antigen in MKN45 gastric carcinoma cells and evaluated the effect of SLe(x) overexpression in cancer cell behavior both in vitro and in vivo using the chicken chorioallantoic membrane (CAM) model. The activation of tyrosine kinase receptors and their downstream molecular targets was also addressed. Our results showed that the expression of ST3GAL4 in MKN45 gastric cancer cells leads to the synthesis of SLe(x) antigens and to an increased invasive phenotype both in vitro and in the in vivo CAM model. Analysis of phosphorylation of tyrosine kinase receptors showed a specific increase in c-Met activation. The characterization of downstream molecular targets of c-Met activation, involved in the invasive phenotype, revealed increased phosphorylation of FAK and Src proteins and activation of Cdc42, Rac1 and RhoA GTPases. Inhibition of c-Met and Src activation abolished the observed increased cell invasive phenotype. In conclusion, the expression of ST3GAL4 leads to SLe(x) antigen expression in gastric cancer cells which in turn induces an increased invasive phenotype through the activation of c-Met, in association with Src, FAK and Cdc42, Rac1 and RhoA GTPases activation. |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23799130/?tool=EBI |
work_keys_str_mv |
AT catarinagomes expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells AT hugoosorio expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells AT martateixeirapinto expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells AT dianacampos expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells AT mariajoseoliveira expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells AT celsoareis expressionofst3gal4leadstoslexexpressionandinducescmetactivationandaninvasivephenotypeingastriccarcinomacells |
_version_ |
1714811821753368576 |