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Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer

BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understo...

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Autores principales: Peyser, Noah D., Pendleton, Kelsey, Gooding, William E., Lui, Vivian W. Y., Johnson, Daniel E., Grandis, Jennifer R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113908/
https://www.ncbi.nlm.nih.gov/pubmed/27855189
http://dx.doi.org/10.1371/journal.pone.0166185
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author Peyser, Noah D.
Pendleton, Kelsey
Gooding, William E.
Lui, Vivian W. Y.
Johnson, Daniel E.
Grandis, Jennifer R.
author_facet Peyser, Noah D.
Pendleton, Kelsey
Gooding, William E.
Lui, Vivian W. Y.
Johnson, Daniel E.
Grandis, Jennifer R.
author_sort Peyser, Noah D.
collection PubMed
description BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). METHODS AND FINDINGS: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression. CONCLUSIONS: These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations.
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spelling pubmed-51139082016-12-08 Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer Peyser, Noah D. Pendleton, Kelsey Gooding, William E. Lui, Vivian W. Y. Johnson, Daniel E. Grandis, Jennifer R. PLoS One Research Article BACKGROUND: Hyperactivation of STAT3 via constitutive phosphorylation of tyrosine 705 (Y705) is common in most human cancers, including head and neck squamous carcinoma (HNSCC). STAT3 is rarely mutated in cancer and the (epi)genetic alterations that lead to STAT3 activation are incompletely understood. Here we used an unbiased approach to identify genomic and epigenomic changes associated with pSTAT3(Y705) expression using data generated by The Cancer Genome Atlas (TCGA). METHODS AND FINDINGS: Mutation, mRNA expression, promoter methylation, and copy number alteration data were extracted from TCGA and examined in the context of pSTAT3(Y705) protein expression. mRNA expression levels of 1279 genes were found to be associated with pSTAT3(705) expression. Association of pSTAT3(Y705) expression with caspase-8 mRNA expression was validated by immunoblot analysis in HNSCC cells. Mutation, promoter hypermethylation, and copy number alteration of any gene were not significantly associated with increased pSTAT3(Y705) protein expression. CONCLUSIONS: These cumulative results suggest that unbiased approaches may be useful in identifying the molecular underpinnings of oncogenic signaling, including STAT3 activation, in HNSCC. Larger datasets will likely be necessary to elucidate signaling consequences of infrequent alterations. Public Library of Science 2016-11-17 /pmc/articles/PMC5113908/ /pubmed/27855189 http://dx.doi.org/10.1371/journal.pone.0166185 Text en © 2016 Peyser et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Peyser, Noah D.
Pendleton, Kelsey
Gooding, William E.
Lui, Vivian W. Y.
Johnson, Daniel E.
Grandis, Jennifer R.
Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title_full Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title_fullStr Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title_full_unstemmed Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title_short Genomic and Transcriptomic Alterations Associated with STAT3 Activation in Head and Neck Cancer
title_sort genomic and transcriptomic alterations associated with stat3 activation in head and neck cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5113908/
https://www.ncbi.nlm.nih.gov/pubmed/27855189
http://dx.doi.org/10.1371/journal.pone.0166185
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