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Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis
Metastatic oral squamous cell carcinoma (OSCC) is frequently associated with recurrent gene abnormalities at specific chromosomal loci. Here, we utilized array comparative genomic hybridization and genome-wide screening of metastatic and non-metastatic tongue tumors to investigate genes potentially...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673138/ https://www.ncbi.nlm.nih.gov/pubmed/26110570 |
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author | da Silva, Sabrina Daniela Marchi, Fabio Albuquerque Xu, Bin Bijian, Krikor Alobaid, Faisal Mlynarek, Alex Rogatto, Silvia Regina Hier, Michael Kowalski, Luiz Paulo Alaoui-Jamali, Moulay A. |
author_facet | da Silva, Sabrina Daniela Marchi, Fabio Albuquerque Xu, Bin Bijian, Krikor Alobaid, Faisal Mlynarek, Alex Rogatto, Silvia Regina Hier, Michael Kowalski, Luiz Paulo Alaoui-Jamali, Moulay A. |
author_sort | da Silva, Sabrina Daniela |
collection | PubMed |
description | Metastatic oral squamous cell carcinoma (OSCC) is frequently associated with recurrent gene abnormalities at specific chromosomal loci. Here, we utilized array comparative genomic hybridization and genome-wide screening of metastatic and non-metastatic tongue tumors to investigate genes potentially contributing to OSCC progression to metastasis. We identified predominant amplifications of chromosomal regions that encompass the RAB5, RAB7 and RAB11 genes (3p24-p22, 3q21.3 and 8p11–12, respectively) in metastatic OSCC. The expression of these Rab GTPases was confirmed by immunohistochemistry in OSCC tissues from a cohort of patients with a follow-up of 10 years. A significant overexpression of Rab5, Rab7 and Rab11 was observed in advanced OSCC cases and co-overexpression of these Rabs was predictive of poor survival (log-rank test, P = 0.006). We generated a Rab interaction network and identified central Rab interactions of relevance to metastasis signaling, including focal adhesion proteins. In preclinical models, mRNA and protein expression levels of these Rab members were elevated in a panel of invasive OSCC cell lines, and their down-regulation prevented cell invasion at least in part via inhibition of focal adhesion disassembly. In summary, our results provide insights into the cooperative role of Rab gene amplifications in OSCC progression and support their potential utility as prognostic markers and therapeutic approach for advanced OSCC. |
format | Online Article Text |
id | pubmed-4673138 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-46731382015-12-23 Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis da Silva, Sabrina Daniela Marchi, Fabio Albuquerque Xu, Bin Bijian, Krikor Alobaid, Faisal Mlynarek, Alex Rogatto, Silvia Regina Hier, Michael Kowalski, Luiz Paulo Alaoui-Jamali, Moulay A. Oncotarget Research Paper Metastatic oral squamous cell carcinoma (OSCC) is frequently associated with recurrent gene abnormalities at specific chromosomal loci. Here, we utilized array comparative genomic hybridization and genome-wide screening of metastatic and non-metastatic tongue tumors to investigate genes potentially contributing to OSCC progression to metastasis. We identified predominant amplifications of chromosomal regions that encompass the RAB5, RAB7 and RAB11 genes (3p24-p22, 3q21.3 and 8p11–12, respectively) in metastatic OSCC. The expression of these Rab GTPases was confirmed by immunohistochemistry in OSCC tissues from a cohort of patients with a follow-up of 10 years. A significant overexpression of Rab5, Rab7 and Rab11 was observed in advanced OSCC cases and co-overexpression of these Rabs was predictive of poor survival (log-rank test, P = 0.006). We generated a Rab interaction network and identified central Rab interactions of relevance to metastasis signaling, including focal adhesion proteins. In preclinical models, mRNA and protein expression levels of these Rab members were elevated in a panel of invasive OSCC cell lines, and their down-regulation prevented cell invasion at least in part via inhibition of focal adhesion disassembly. In summary, our results provide insights into the cooperative role of Rab gene amplifications in OSCC progression and support their potential utility as prognostic markers and therapeutic approach for advanced OSCC. Impact Journals LLC 2015-06-15 /pmc/articles/PMC4673138/ /pubmed/26110570 Text en Copyright: © 2015 da Silva 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 da Silva, Sabrina Daniela Marchi, Fabio Albuquerque Xu, Bin Bijian, Krikor Alobaid, Faisal Mlynarek, Alex Rogatto, Silvia Regina Hier, Michael Kowalski, Luiz Paulo Alaoui-Jamali, Moulay A. Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title | Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title_full | Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title_fullStr | Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title_full_unstemmed | Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title_short | Predominant Rab-GTPase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
title_sort | predominant rab-gtpase amplicons contributing to oral squamous cell carcinoma progression to metastasis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4673138/ https://www.ncbi.nlm.nih.gov/pubmed/26110570 |
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