Cargando…
Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells
Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the α(1,...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418920/ https://www.ncbi.nlm.nih.gov/pubmed/37569254 http://dx.doi.org/10.3390/ijms241511879 |
_version_ | 1785088384678494208 |
---|---|
author | López-Cortés, Rubén Correa Pardo, Isabel Muinelo-Romay, Laura Fernández-Briera, Almudena Gil-Martín, Emilio |
author_facet | López-Cortés, Rubén Correa Pardo, Isabel Muinelo-Romay, Laura Fernández-Briera, Almudena Gil-Martín, Emilio |
author_sort | López-Cortés, Rubén |
collection | PubMed |
description | Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the α(1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan, or mitomycin C. In contrast, a combination of TRAIL and oxaliplatin, irinotecan, or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC. |
format | Online Article Text |
id | pubmed-10418920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-104189202023-08-12 Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells López-Cortés, Rubén Correa Pardo, Isabel Muinelo-Romay, Laura Fernández-Briera, Almudena Gil-Martín, Emilio Int J Mol Sci Article Epithelial cells can undergo apoptosis by manipulating the balance between pro-survival and apoptotic signals. In this work, we show that TRAIL-induced apoptosis can be differentially regulated by the expression of α(1,6)fucosyltransferase (FucT-8), the only enzyme in mammals that transfers the α(1,6)fucose residue to the pentasaccharide core of complex N-glycans. Specifically, in the cellular model of colorectal cancer (CRC) progression formed using the human syngeneic lines SW480 and SW620, knockdown of the FucT-8-encoding FUT8 gene significantly enhanced TRAIL-induced apoptosis in SW480 cells. However, FUT8 repression did not affect SW620 cells, which suggests that core fucosylation differentiates TRAIL-sensitive premetastatic SW480 cells from TRAIL-resistant metastatic SW620 cells. In this regard, we provide evidence that phosphorylation of ERK1/2 kinases can dynamically regulate TRAIL-dependent apoptosis and that core fucosylation can control the ERK/MAPK pro-survival pathway in which SW480 and SW620 cells participate. Moreover, the depletion of core fucosylation sensitises primary tumour SW480 cells to the combination of TRAIL and low doses of 5-FU, oxaliplatin, irinotecan, or mitomycin C. In contrast, a combination of TRAIL and oxaliplatin, irinotecan, or bevacizumab reinforces resistance of FUT8-knockdown metastatic SW620 cells to apoptosis. Consequently, FucT-8 could be a plausible target for increasing apoptosis and drug response in early CRC. MDPI 2023-07-25 /pmc/articles/PMC10418920/ /pubmed/37569254 http://dx.doi.org/10.3390/ijms241511879 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article López-Cortés, Rubén Correa Pardo, Isabel Muinelo-Romay, Laura Fernández-Briera, Almudena Gil-Martín, Emilio Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title | Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title_full | Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title_fullStr | Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title_full_unstemmed | Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title_short | Core Fucosylation Mediated by the FucT-8 Enzyme Affects TRAIL-Induced Apoptosis and Sensitivity to Chemotherapy in Human SW480 and SW620 Colorectal Cancer Cells |
title_sort | core fucosylation mediated by the fuct-8 enzyme affects trail-induced apoptosis and sensitivity to chemotherapy in human sw480 and sw620 colorectal cancer cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418920/ https://www.ncbi.nlm.nih.gov/pubmed/37569254 http://dx.doi.org/10.3390/ijms241511879 |
work_keys_str_mv | AT lopezcortesruben corefucosylationmediatedbythefuct8enzymeaffectstrailinducedapoptosisandsensitivitytochemotherapyinhumansw480andsw620colorectalcancercells AT correapardoisabel corefucosylationmediatedbythefuct8enzymeaffectstrailinducedapoptosisandsensitivitytochemotherapyinhumansw480andsw620colorectalcancercells AT muineloromaylaura corefucosylationmediatedbythefuct8enzymeaffectstrailinducedapoptosisandsensitivitytochemotherapyinhumansw480andsw620colorectalcancercells AT fernandezbrieraalmudena corefucosylationmediatedbythefuct8enzymeaffectstrailinducedapoptosisandsensitivitytochemotherapyinhumansw480andsw620colorectalcancercells AT gilmartinemilio corefucosylationmediatedbythefuct8enzymeaffectstrailinducedapoptosisandsensitivitytochemotherapyinhumansw480andsw620colorectalcancercells |