Cargando…
FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation
Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl ha...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170636/ https://www.ncbi.nlm.nih.gov/pubmed/25071022 |
_version_ | 1782335840112869376 |
---|---|
author | Ferrari, Luca Pistocchi, Anna Libera, Laura Boari, Nicola Mortini, Pietro Bellipanni, Gianfranco Giordano, Antonio Cotelli, Franco Riva, Paola |
author_facet | Ferrari, Luca Pistocchi, Anna Libera, Laura Boari, Nicola Mortini, Pietro Bellipanni, Gianfranco Giordano, Antonio Cotelli, Franco Riva, Paola |
author_sort | Ferrari, Luca |
collection | PubMed |
description | Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset. |
format | Online Article Text |
id | pubmed-4170636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-41706362014-09-22 FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation Ferrari, Luca Pistocchi, Anna Libera, Laura Boari, Nicola Mortini, Pietro Bellipanni, Gianfranco Giordano, Antonio Cotelli, Franco Riva, Paola Oncotarget Research Paper Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset. Impact Journals LLC 2014-07-01 /pmc/articles/PMC4170636/ /pubmed/25071022 Text en Copyright: © 2014 Ferrari et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Ferrari, Luca Pistocchi, Anna Libera, Laura Boari, Nicola Mortini, Pietro Bellipanni, Gianfranco Giordano, Antonio Cotelli, Franco Riva, Paola FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title | FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title_full | FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title_fullStr | FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title_full_unstemmed | FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title_short | FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
title_sort | fas/fasl are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4170636/ https://www.ncbi.nlm.nih.gov/pubmed/25071022 |
work_keys_str_mv | AT ferrariluca fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT pistocchianna fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT liberalaura fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT boarinicola fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT mortinipietro fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT bellipannigianfranco fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT giordanoantonio fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT cotellifranco fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation AT rivapaola fasfaslaredysregulatedinchordomaandtheirlossoffunctionimpairszebrafishnotochordformation |