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Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of gastrointestinal tract in the world, and the long-term prognosis for ESCC patients still remains dismal due to the lack of effective early diagnosis biomarkers. MATERIALS AND METHODS: Western blot and i...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462166/ https://www.ncbi.nlm.nih.gov/pubmed/31040705 http://dx.doi.org/10.2147/OTT.S180255 |
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author | Zhou, Li Deng, Zhe-Zhi Li, Hai-Yan Jiang, Nan Wei, Zhi-Sheng Hong, Ming-Fan Wang, Ji-Hui Zhang, Ming-Xing Shi, Yi-Hua Lu, Zheng-Qi Huang, Xu-Ming |
author_facet | Zhou, Li Deng, Zhe-Zhi Li, Hai-Yan Jiang, Nan Wei, Zhi-Sheng Hong, Ming-Fan Wang, Ji-Hui Zhang, Ming-Xing Shi, Yi-Hua Lu, Zheng-Qi Huang, Xu-Ming |
author_sort | Zhou, Li |
collection | PubMed |
description | INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of gastrointestinal tract in the world, and the long-term prognosis for ESCC patients still remains dismal due to the lack of effective early diagnosis biomarkers. MATERIALS AND METHODS: Western blot and immunochemistry were used to determine the expression of PRR11 in 201 clinicopathologically characterized ESCC specimens. The effects of PRR11 on stem cell-like traits and tumorigenicity were examined by tumor sphere formation assay and SP assays in vitro and by a tumorigenesis model in vivo. The mechanism by which PRR11 mediated Wnt/β-catenin signaling was explored using luciferase reporter, immuno-chemistry, and real time-PCR (RT-PCR) assays. RESULTS: We found that PRR11 was markedly upregulated, at the level of both transcription and translation, in ESCC cell lines as compared with normal esophageal epithelial cells (NECCs). Immunohistochemical analysis showed that 69.2% paraffin-embedded archival ESCC specimens exhibited high levels of PRR11 expression, and multivariate analysis revealed that PRR11 upregulation might be an independent prognostic indicator for the survival of patients with ESCC. Furthermore, overexpression of PRR11 dramatically enhanced, whereas inhibition of PRR11 reduced the capability of cancer stem cell (CSC)-like phenotypes and tumorigenicity of ESCC cells both in vitro and in vivo. Mechanically, we demonstrated PRR11-enhanced tumorigenicity of ESCC cells via activating Wnt/β-catenin signaling, and PRR11 expression is found to be significantly correlated with β-catenin nuclear location in ESCC. CONCLUSION: Our findings suggest that the PRR11 might represent a novel and valuable prognostic marker for ESCC progression and play a role during the development and progression of this malignancy. |
format | Online Article Text |
id | pubmed-6462166 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-64621662019-04-30 Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma Zhou, Li Deng, Zhe-Zhi Li, Hai-Yan Jiang, Nan Wei, Zhi-Sheng Hong, Ming-Fan Wang, Ji-Hui Zhang, Ming-Xing Shi, Yi-Hua Lu, Zheng-Qi Huang, Xu-Ming Onco Targets Ther Original Research INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies of gastrointestinal tract in the world, and the long-term prognosis for ESCC patients still remains dismal due to the lack of effective early diagnosis biomarkers. MATERIALS AND METHODS: Western blot and immunochemistry were used to determine the expression of PRR11 in 201 clinicopathologically characterized ESCC specimens. The effects of PRR11 on stem cell-like traits and tumorigenicity were examined by tumor sphere formation assay and SP assays in vitro and by a tumorigenesis model in vivo. The mechanism by which PRR11 mediated Wnt/β-catenin signaling was explored using luciferase reporter, immuno-chemistry, and real time-PCR (RT-PCR) assays. RESULTS: We found that PRR11 was markedly upregulated, at the level of both transcription and translation, in ESCC cell lines as compared with normal esophageal epithelial cells (NECCs). Immunohistochemical analysis showed that 69.2% paraffin-embedded archival ESCC specimens exhibited high levels of PRR11 expression, and multivariate analysis revealed that PRR11 upregulation might be an independent prognostic indicator for the survival of patients with ESCC. Furthermore, overexpression of PRR11 dramatically enhanced, whereas inhibition of PRR11 reduced the capability of cancer stem cell (CSC)-like phenotypes and tumorigenicity of ESCC cells both in vitro and in vivo. Mechanically, we demonstrated PRR11-enhanced tumorigenicity of ESCC cells via activating Wnt/β-catenin signaling, and PRR11 expression is found to be significantly correlated with β-catenin nuclear location in ESCC. CONCLUSION: Our findings suggest that the PRR11 might represent a novel and valuable prognostic marker for ESCC progression and play a role during the development and progression of this malignancy. Dove Medical Press 2019-04-09 /pmc/articles/PMC6462166/ /pubmed/31040705 http://dx.doi.org/10.2147/OTT.S180255 Text en © 2019 Zhou et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research Zhou, Li Deng, Zhe-Zhi Li, Hai-Yan Jiang, Nan Wei, Zhi-Sheng Hong, Ming-Fan Wang, Ji-Hui Zhang, Ming-Xing Shi, Yi-Hua Lu, Zheng-Qi Huang, Xu-Ming Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title | Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title_full | Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title_fullStr | Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title_full_unstemmed | Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title_short | Overexpression of PRR11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
title_sort | overexpression of prr11 promotes tumorigenic capability and is associated with progression in esophageal squamous cell carcinoma |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462166/ https://www.ncbi.nlm.nih.gov/pubmed/31040705 http://dx.doi.org/10.2147/OTT.S180255 |
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