Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Gurbi, Bianka, Brauswetter, Diána, Pénzes, Kinga, Varga, Attila, Krenács, Tibor, Dános, Kornél, Birtalan, Ede, Tamás, László, Csala, Miklós
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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
_version_ 1784886442609082368
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
work_keys_str_mv AT gurbibianka mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT brauswetterdiana mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT penzeskinga mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT vargaattila mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT krenacstibor mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT danoskornel mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT birtalanede mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT tamaslaszlo mekisapotentialindirecttargetinsubtypesofheadandneckcancers
AT csalamiklos mekisapotentialindirecttargetinsubtypesofheadandneckcancers