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The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer
Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53) Our recent work has id...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410280/ https://www.ncbi.nlm.nih.gov/pubmed/28160562 http://dx.doi.org/10.18632/oncotarget.14967 |
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author | Coaxum, Sonya D. Tiedeken, Jessica Garrett-Mayer, Elizabeth Myers, Jeffrey Rosenzweig, Steven A. Neskey, David M. |
author_facet | Coaxum, Sonya D. Tiedeken, Jessica Garrett-Mayer, Elizabeth Myers, Jeffrey Rosenzweig, Steven A. Neskey, David M. |
author_sort | Coaxum, Sonya D. |
collection | PubMed |
description | Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53) Our recent work has identified an approach to stratify patients with tumors harboring high or low risk TP53 mutations. Non-muscle Myosin IIA (NMIIA) was recently identified as a tumor suppressor in HNSCC. We now demonstrate that low MYH9 expression is associated with decreased survival in patients with head and neck cancer harboring low-risk mutp53 but not high-risk mutp53. Furthermore, inhibition of NMIIA leads to increased invasion in cells harboring wildtype p53 (wtp53), which was not observed in high-risk mutp53 cells. This increased invasiveness of wtp53 following NMIIA inhibition was associated with reduced p53 target gene expression and was absent in cells expressing mutp53. This reduced expression may be due, in part, to a decrease in nuclear localization of wtp53. These findings suggest that the tumor suppressor capability of wtp53 is dependent upon functional NMIIA and that the invasive phenotype of high-risk mutp53 is independent of NMIIA. |
format | Online Article Text |
id | pubmed-5410280 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54102802017-05-04 The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer Coaxum, Sonya D. Tiedeken, Jessica Garrett-Mayer, Elizabeth Myers, Jeffrey Rosenzweig, Steven A. Neskey, David M. Oncotarget Research Paper Over 300,000 patients develop squamous cell carcinoma of the head and neck (HNSCC) worldwide with 25-30% of patients ultimately dying from their disease. Currently, molecular biomarkers are not used in HNSCC but several genes have been identified including mutant TP53 (mutp53) Our recent work has identified an approach to stratify patients with tumors harboring high or low risk TP53 mutations. Non-muscle Myosin IIA (NMIIA) was recently identified as a tumor suppressor in HNSCC. We now demonstrate that low MYH9 expression is associated with decreased survival in patients with head and neck cancer harboring low-risk mutp53 but not high-risk mutp53. Furthermore, inhibition of NMIIA leads to increased invasion in cells harboring wildtype p53 (wtp53), which was not observed in high-risk mutp53 cells. This increased invasiveness of wtp53 following NMIIA inhibition was associated with reduced p53 target gene expression and was absent in cells expressing mutp53. This reduced expression may be due, in part, to a decrease in nuclear localization of wtp53. These findings suggest that the tumor suppressor capability of wtp53 is dependent upon functional NMIIA and that the invasive phenotype of high-risk mutp53 is independent of NMIIA. Impact Journals LLC 2017-02-01 /pmc/articles/PMC5410280/ /pubmed/28160562 http://dx.doi.org/10.18632/oncotarget.14967 Text en Copyright: © 2017 Coaxum et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Coaxum, Sonya D. Tiedeken, Jessica Garrett-Mayer, Elizabeth Myers, Jeffrey Rosenzweig, Steven A. Neskey, David M. The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title | The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title_full | The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title_fullStr | The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title_full_unstemmed | The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title_short | The tumor suppressor capability of p53 is dependent on non-muscle myosin IIA function in head and neck cancer |
title_sort | tumor suppressor capability of p53 is dependent on non-muscle myosin iia function in head and neck cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410280/ https://www.ncbi.nlm.nih.gov/pubmed/28160562 http://dx.doi.org/10.18632/oncotarget.14967 |
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