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EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy
Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to an...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482801/ https://www.ncbi.nlm.nih.gov/pubmed/32929368 http://dx.doi.org/10.7150/thno.47176 |
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author | Liu, Shuli Wang, Yang Han, Yong Xia, Weiya Zhang, Ling Xu, Shengming Ju, Houyu Zhang, Xiangkai Ren, Guoxin Liu, Liu Ye, Weimin Zhang, Zhiyuan Hu, Jingzhou |
author_facet | Liu, Shuli Wang, Yang Han, Yong Xia, Weiya Zhang, Ling Xu, Shengming Ju, Houyu Zhang, Xiangkai Ren, Guoxin Liu, Liu Ye, Weimin Zhang, Zhiyuan Hu, Jingzhou |
author_sort | Liu, Shuli |
collection | PubMed |
description | Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to analyze expression of EREG in HNSCC tissues. Immunoblotting was performed to identify the EGFR-mediated pathways altered by EREG. The role of EREG in oncogenesis was investigated in vivo and in vitro. Results: Upregulated EREG expression predicted a poor prognosis and triggered HNSCC oncogenic transformation by activating the epidermal growth factor receptor (EGFR) signaling pathway. We also demonstrated the direct association of EREG with EGFR and that this binding required EGFR domains I and III and the N57 residue of EREG. Moreover, EREG overexpression was shown to promote HNSCC oncogenesis by inducing C-Myc expression, and the pharmacological inhibition of C-Myc rescued EREG-promoted HNSCC oncogenesis. Unlike other EGFR ligands, EREG could mimic EGFR mutations by sustaining the activation of the EGFR-Erk pathway, and high EREG expression was positively associated with the response to treatment with the EGFR inhibitor erlotinib. Furthermore, knockdown of EREG decreased sensitivity to erlotinib treatment in vitro and in vivo. Conclusions: These results identify the EREG-EGFR-C-Myc pathway as a crucial axis that drives HNSCC oncogenesis and show that EREG expression could be a predictive functional marker of sensitivity to erlotinib therapy in HNSCC. |
format | Online Article Text |
id | pubmed-7482801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-74828012020-09-13 EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy Liu, Shuli Wang, Yang Han, Yong Xia, Weiya Zhang, Ling Xu, Shengming Ju, Houyu Zhang, Xiangkai Ren, Guoxin Liu, Liu Ye, Weimin Zhang, Zhiyuan Hu, Jingzhou Theranostics Research Paper Rationale: The oncogenesis of head and neck squamous cell carcinoma (HNSCC) is believed to result from oncogene activation and tumor suppressor inactivation. Here, we identified a new oncogenic role for the EREG gene in HNSCC. Methods: The TCGA database and immunohistochemistry assay were used to analyze expression of EREG in HNSCC tissues. Immunoblotting was performed to identify the EGFR-mediated pathways altered by EREG. The role of EREG in oncogenesis was investigated in vivo and in vitro. Results: Upregulated EREG expression predicted a poor prognosis and triggered HNSCC oncogenic transformation by activating the epidermal growth factor receptor (EGFR) signaling pathway. We also demonstrated the direct association of EREG with EGFR and that this binding required EGFR domains I and III and the N57 residue of EREG. Moreover, EREG overexpression was shown to promote HNSCC oncogenesis by inducing C-Myc expression, and the pharmacological inhibition of C-Myc rescued EREG-promoted HNSCC oncogenesis. Unlike other EGFR ligands, EREG could mimic EGFR mutations by sustaining the activation of the EGFR-Erk pathway, and high EREG expression was positively associated with the response to treatment with the EGFR inhibitor erlotinib. Furthermore, knockdown of EREG decreased sensitivity to erlotinib treatment in vitro and in vivo. Conclusions: These results identify the EREG-EGFR-C-Myc pathway as a crucial axis that drives HNSCC oncogenesis and show that EREG expression could be a predictive functional marker of sensitivity to erlotinib therapy in HNSCC. Ivyspring International Publisher 2020-08-25 /pmc/articles/PMC7482801/ /pubmed/32929368 http://dx.doi.org/10.7150/thno.47176 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Liu, Shuli Wang, Yang Han, Yong Xia, Weiya Zhang, Ling Xu, Shengming Ju, Houyu Zhang, Xiangkai Ren, Guoxin Liu, Liu Ye, Weimin Zhang, Zhiyuan Hu, Jingzhou EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title | EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title_full | EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title_fullStr | EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title_full_unstemmed | EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title_short | EREG-driven oncogenesis of Head and Neck Squamous Cell Carcinoma exhibits higher sensitivity to Erlotinib therapy |
title_sort | ereg-driven oncogenesis of head and neck squamous cell carcinoma exhibits higher sensitivity to erlotinib therapy |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482801/ https://www.ncbi.nlm.nih.gov/pubmed/32929368 http://dx.doi.org/10.7150/thno.47176 |
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