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MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers
The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917750/ https://www.ncbi.nlm.nih.gov/pubmed/36769112 http://dx.doi.org/10.3390/ijms24032782 |
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author | Gurbi, Bianka Brauswetter, Diána Pénzes, Kinga Varga, Attila Krenács, Tibor Dános, Kornél Birtalan, Ede Tamás, László Csala, Miklós |
author_facet | Gurbi, Bianka Brauswetter, Diána Pénzes, Kinga Varga, Attila Krenács, Tibor Dános, Kornél Birtalan, Ede Tamás, László Csala, Miklós |
author_sort | Gurbi, Bianka |
collection | PubMed |
description | The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our research was performed on three human papillomavirus (HPV)-negative HNSCC-cell lines: Detroit 562, FaDu and SCC25. Changes in cell viability upon EGFR and/or MEK inhibitors were measured by the MTT method. The protein-expression and phosphorylation profiles of the EGFR-initiated signaling pathways were assessed using Western-blot analysis. The EGFR expression and pY1068-EGFR levels were also studied in the patient-derived HNSCC samples. We found significant differences between the sensitivity of the tumor-cell lines used. The SCC25 line was found to be the most sensitive to the MEK inhibitors, possibly due to the lack of feedback Akt activation through EGFR. By contrast, this feedback activation had an important role in the FaDu cells. The observed insensitivity of the Detroit 562 cells to the MEK inhibitors might have been caused by their PIK3CA mutation. Among HNSCC cell lines, EGFR-initiated signaling pathways are particularly versatile. An ERK/EGFR feedback loop can lead to Akt-pathway activation upon MEK inhibition, and it is related not only to increased amounts of EGFR but also to the elevation of pY1068-EGFR levels. The presence of this mechanism may justify the combined application of EGFR and MEK inhibitors. |
format | Online Article Text |
id | pubmed-9917750 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-99177502023-02-11 MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers Gurbi, Bianka Brauswetter, Diána Pénzes, Kinga Varga, Attila Krenács, Tibor Dános, Kornél Birtalan, Ede Tamás, László Csala, Miklós Int J Mol Sci Article The poor prognosis of head-and-neck squamous cell carcinoma (HNSCC) is partly due to the lack of reliable prognostic and predictive markers. The Ras/Raf/MEK/ERK signaling pathway is often activated by overexpressed epidermal growth factor receptor (EGFR) and stimulates the progression of HNSCCs. Our research was performed on three human papillomavirus (HPV)-negative HNSCC-cell lines: Detroit 562, FaDu and SCC25. Changes in cell viability upon EGFR and/or MEK inhibitors were measured by the MTT method. The protein-expression and phosphorylation profiles of the EGFR-initiated signaling pathways were assessed using Western-blot analysis. The EGFR expression and pY1068-EGFR levels were also studied in the patient-derived HNSCC samples. We found significant differences between the sensitivity of the tumor-cell lines used. The SCC25 line was found to be the most sensitive to the MEK inhibitors, possibly due to the lack of feedback Akt activation through EGFR. By contrast, this feedback activation had an important role in the FaDu cells. The observed insensitivity of the Detroit 562 cells to the MEK inhibitors might have been caused by their PIK3CA mutation. Among HNSCC cell lines, EGFR-initiated signaling pathways are particularly versatile. An ERK/EGFR feedback loop can lead to Akt-pathway activation upon MEK inhibition, and it is related not only to increased amounts of EGFR but also to the elevation of pY1068-EGFR levels. The presence of this mechanism may justify the combined application of EGFR and MEK inhibitors. MDPI 2023-02-01 /pmc/articles/PMC9917750/ /pubmed/36769112 http://dx.doi.org/10.3390/ijms24032782 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gurbi, Bianka Brauswetter, Diána Pénzes, Kinga Varga, Attila Krenács, Tibor Dános, Kornél Birtalan, Ede Tamás, László Csala, Miklós MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title | MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title_full | MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title_fullStr | MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title_full_unstemmed | MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title_short | MEK Is a Potential Indirect Target in Subtypes of Head and Neck Cancers |
title_sort | mek is a potential indirect target in subtypes of head and neck cancers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917750/ https://www.ncbi.nlm.nih.gov/pubmed/36769112 http://dx.doi.org/10.3390/ijms24032782 |
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