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Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling
Hypopharyngeal cancer (HPC) frequently presents at an advanced stage and displays early submucosal spread, resulting in a poor prognosis. It is among the worst of all cancers in the head and neck subsites. Therefore, detection of HPC at an earlier stage would be beneficial to patients. In this study...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cognizant Communication Corporation
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841079/ https://www.ncbi.nlm.nih.gov/pubmed/28276321 http://dx.doi.org/10.3727/096504017X14886420642823 |
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author | Wu, Ping Quan, Huatao Kang, Jing He, Jian Luo, Shi Xie, Chubo Xu, Jing Tang, Yaoyun Zhao, Suping |
author_facet | Wu, Ping Quan, Huatao Kang, Jing He, Jian Luo, Shi Xie, Chubo Xu, Jing Tang, Yaoyun Zhao, Suping |
author_sort | Wu, Ping |
collection | PubMed |
description | Hypopharyngeal cancer (HPC) frequently presents at an advanced stage and displays early submucosal spread, resulting in a poor prognosis. It is among the worst of all cancers in the head and neck subsites. Therefore, detection of HPC at an earlier stage would be beneficial to patients. In this study, we used differential in-gel electrophoresis (DIGE) and two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics analysis to identify the potential biomarkers for HPC. Among the differential proteins identified, calcium-binding protein S100A9 was overexpressed in HPC tissues compared with normal adjacent tissues, and S100A9 expression in metastatic tissues and advanced tumor tissues was higher than in nonmetastatic tissues and early tumor tissues. S100A9 expression was further confirmed in a large additional cohort. Our data showed that a higher S100A9 level was associated with a poor prognosis for HPC patients, and this may be an independent factor for predicting their prognosis. In addition, S100A9 protein expression was upregulated in human HPC cell lines compared with normal oral cavity epithelia. Knockdown of S100A9 induced significant inhibition of cell growth and their invasive ability. Mechanically, we found that downregulation of S100A9 significantly reduced the expression of NF-κB, phosphorylation of NF-κB and Bcl-2, as well as the expression of MMP7 and MMP2. Restoration of NF-κB expression sufficiently reversed the inhibitory effects on cell proliferation and invasion induced by S100A9 downregulation in vitro and in vivo. In conclusion, for the first time, we have identified S100A9 as an independent prognostic factor for HPC. Inhibiting S100A9 expression would be a potential novel diagnostic biomarker and therapeutic target for HPC treatment. |
format | Online Article Text |
id | pubmed-7841079 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cognizant Communication Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-78410792021-02-16 Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling Wu, Ping Quan, Huatao Kang, Jing He, Jian Luo, Shi Xie, Chubo Xu, Jing Tang, Yaoyun Zhao, Suping Oncol Res Article Hypopharyngeal cancer (HPC) frequently presents at an advanced stage and displays early submucosal spread, resulting in a poor prognosis. It is among the worst of all cancers in the head and neck subsites. Therefore, detection of HPC at an earlier stage would be beneficial to patients. In this study, we used differential in-gel electrophoresis (DIGE) and two-dimensional polyacrylamide gel electrophoresis (2-DE) proteomics analysis to identify the potential biomarkers for HPC. Among the differential proteins identified, calcium-binding protein S100A9 was overexpressed in HPC tissues compared with normal adjacent tissues, and S100A9 expression in metastatic tissues and advanced tumor tissues was higher than in nonmetastatic tissues and early tumor tissues. S100A9 expression was further confirmed in a large additional cohort. Our data showed that a higher S100A9 level was associated with a poor prognosis for HPC patients, and this may be an independent factor for predicting their prognosis. In addition, S100A9 protein expression was upregulated in human HPC cell lines compared with normal oral cavity epithelia. Knockdown of S100A9 induced significant inhibition of cell growth and their invasive ability. Mechanically, we found that downregulation of S100A9 significantly reduced the expression of NF-κB, phosphorylation of NF-κB and Bcl-2, as well as the expression of MMP7 and MMP2. Restoration of NF-κB expression sufficiently reversed the inhibitory effects on cell proliferation and invasion induced by S100A9 downregulation in vitro and in vivo. In conclusion, for the first time, we have identified S100A9 as an independent prognostic factor for HPC. Inhibiting S100A9 expression would be a potential novel diagnostic biomarker and therapeutic target for HPC treatment. Cognizant Communication Corporation 2017-11-02 /pmc/articles/PMC7841079/ /pubmed/28276321 http://dx.doi.org/10.3727/096504017X14886420642823 Text en Copyright © 2017 Cognizant, LLC. http://creativecommons.org/licenses/by-nc-nd/4.0/ This article is licensed under a Creative Commons Attribution-NonCommercial NoDerivatives 4.0 International License. |
spellingShingle | Article Wu, Ping Quan, Huatao Kang, Jing He, Jian Luo, Shi Xie, Chubo Xu, Jing Tang, Yaoyun Zhao, Suping Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title | Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title_full | Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title_fullStr | Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title_full_unstemmed | Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title_short | Downregulation of Calcium-Binding Protein S100A9 Inhibits Hypopharyngeal Cancer Cell Proliferation and Invasion Ability Through Inactivation of NF-κB Signaling |
title_sort | downregulation of calcium-binding protein s100a9 inhibits hypopharyngeal cancer cell proliferation and invasion ability through inactivation of nf-κb signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841079/ https://www.ncbi.nlm.nih.gov/pubmed/28276321 http://dx.doi.org/10.3727/096504017X14886420642823 |
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