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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

Tumor promoting effects of CD95 signaling in chemoresistant cells

Authors: Elisabet Ametller, Susana García-Recio, Domizziana Costamagna, Cristina Mayordomo, Patricia Fernández-Nogueira, Neus Carbó, Eva María Pastor-Arroyo, Pedro Gascón, Vanessa Almendro

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. The aim of this study was to characterize some key cellular responses controlled by CD95 signaling in oxaliplatin-resistant colon cancer cells.

Results

We show that CD95 triggering results in an increased metastatic ability in resistant cells. Moreover, oxaliplatin treatment itself stimulates cell migration and decreases cell adhesion through CD95 activation, since CD95 expression inhibition by siRNA blocks the promigratory effects of oxaliplatin. These promigratory effects are related to the epithelia-to-mesenchymal transition (EMT) phenomenon, as evidenced by the up-regulation of some transcription factors and mesenchymal markers both in vitro and in vivo.

Conclusions

We conclude that oxaliplatin treatment in cells that have acquired resistance to oxaliplatin-induced apoptosis results in tumor-promoting effects through the activation of CD95 signaling and by inducing EMT, all these events jointly contributing to a metastatic phenotype.
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Metadata
Title
Tumor promoting effects of CD95 signaling in chemoresistant cells
Authors
Elisabet Ametller
Susana García-Recio
Domizziana Costamagna
Cristina Mayordomo
Patricia Fernández-Nogueira
Neus Carbó
Eva María Pastor-Arroyo
Pedro Gascón
Vanessa Almendro
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-161

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