Cargando…
Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors
Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma with poor prognosis due to their complex genetic changes, invasive growth, and insensitivity to chemo- and radiotherapies. One of the most frequently lost chromosome arms in human MPNSTs is chromosome 9p. However, the cancer dri...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955097/ https://www.ncbi.nlm.nih.gov/pubmed/29805750 http://dx.doi.org/10.18632/oncotarget.25236 |
_version_ | 1783323641465798656 |
---|---|
author | Kumari, Rashmi Silic, Martin R. Jones-Hall, Yava L. Nin-Velez, Alexandra Yang, Jer-Yen Mittal, Suresh K. Zhang, GuangJun |
author_facet | Kumari, Rashmi Silic, Martin R. Jones-Hall, Yava L. Nin-Velez, Alexandra Yang, Jer-Yen Mittal, Suresh K. Zhang, GuangJun |
author_sort | Kumari, Rashmi |
collection | PubMed |
description | Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma with poor prognosis due to their complex genetic changes, invasive growth, and insensitivity to chemo- and radiotherapies. One of the most frequently lost chromosome arms in human MPNSTs is chromosome 9p. However, the cancer driver genes located on it remain largely unknown, except the tumor suppressor gene, p16 (INK4)/CDKN2A. Previously, we identified RECK as a tumor suppressor gene candidate on chromosome 9p using zebrafish-human comparative oncogenomics. In this study, we investigated the tumorigenesis of the reck gene using zebrafish genetic models in both tp53 and ribosomal protein gene mutation background. We also examined the biological effects of RECK gene restoration in human MPNST cell lines. These results provide the first genetic evidence that reck is a bona fide tumor suppressor gene for MPNSTs in zebrafish. In addition, restoration of the RECK gene in human MPNST cells leads to growth inhibition suggesting that the reactivation of RECK could serve as a potential therapeutic strategy for MPNSTs. |
format | Online Article Text |
id | pubmed-5955097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59550972018-05-27 Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors Kumari, Rashmi Silic, Martin R. Jones-Hall, Yava L. Nin-Velez, Alexandra Yang, Jer-Yen Mittal, Suresh K. Zhang, GuangJun Oncotarget Research Paper Malignant peripheral nerve sheath tumors (MPNSTs) are a type of sarcoma with poor prognosis due to their complex genetic changes, invasive growth, and insensitivity to chemo- and radiotherapies. One of the most frequently lost chromosome arms in human MPNSTs is chromosome 9p. However, the cancer driver genes located on it remain largely unknown, except the tumor suppressor gene, p16 (INK4)/CDKN2A. Previously, we identified RECK as a tumor suppressor gene candidate on chromosome 9p using zebrafish-human comparative oncogenomics. In this study, we investigated the tumorigenesis of the reck gene using zebrafish genetic models in both tp53 and ribosomal protein gene mutation background. We also examined the biological effects of RECK gene restoration in human MPNST cell lines. These results provide the first genetic evidence that reck is a bona fide tumor suppressor gene for MPNSTs in zebrafish. In addition, restoration of the RECK gene in human MPNST cells leads to growth inhibition suggesting that the reactivation of RECK could serve as a potential therapeutic strategy for MPNSTs. Impact Journals LLC 2018-05-04 /pmc/articles/PMC5955097/ /pubmed/29805750 http://dx.doi.org/10.18632/oncotarget.25236 Text en Copyright: © 2018 Kumari et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Kumari, Rashmi Silic, Martin R. Jones-Hall, Yava L. Nin-Velez, Alexandra Yang, Jer-Yen Mittal, Suresh K. Zhang, GuangJun Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title | Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title_full | Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title_fullStr | Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title_full_unstemmed | Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title_short | Identification of RECK as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
title_sort | identification of reck as an evolutionarily conserved tumor suppressor gene for zebrafish malignant peripheral nerve sheath tumors |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5955097/ https://www.ncbi.nlm.nih.gov/pubmed/29805750 http://dx.doi.org/10.18632/oncotarget.25236 |
work_keys_str_mv | AT kumarirashmi identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT silicmartinr identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT joneshallyaval identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT ninvelezalexandra identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT yangjeryen identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT mittalsureshk identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors AT zhangguangjun identificationofreckasanevolutionarilyconservedtumorsuppressorgeneforzebrafishmalignantperipheralnervesheathtumors |