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BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression
SIMPLE SUMMARY: Bruton’s Tyrosine Kinase (BTK) was originally considered to be primarily expressed in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, elevated expression of novel BTK isoforms of 80 and 65 kDa have been recently described for several solid...
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/PMC9818583/ https://www.ncbi.nlm.nih.gov/pubmed/36612306 http://dx.doi.org/10.3390/cancers15010310 |
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author | Betzler, Annika C. Strobel, Hannah Abou Kors, Tsima Ezić, Jasmin Lesakova, Kristina Pscheid, Ronja Azoitei, Ninel Sporleder, Johanna Staufenberg, Anna-Rebekka Drees, Robert Weissinger, Stephanie E. Greve, Jens Doescher, Johannes Theodoraki, Marie-Nicole Schuler, Patrick J. Laban, Simon Kibe, Toshiro Kishida, Michiko Kishida, Shosei Idel, Christian Hoffmann, Thomas K. Lavitrano, Marialuisa Grassilli, Emanuela Brunner, Cornelia |
author_facet | Betzler, Annika C. Strobel, Hannah Abou Kors, Tsima Ezić, Jasmin Lesakova, Kristina Pscheid, Ronja Azoitei, Ninel Sporleder, Johanna Staufenberg, Anna-Rebekka Drees, Robert Weissinger, Stephanie E. Greve, Jens Doescher, Johannes Theodoraki, Marie-Nicole Schuler, Patrick J. Laban, Simon Kibe, Toshiro Kishida, Michiko Kishida, Shosei Idel, Christian Hoffmann, Thomas K. Lavitrano, Marialuisa Grassilli, Emanuela Brunner, Cornelia |
author_sort | Betzler, Annika C. |
collection | PubMed |
description | SIMPLE SUMMARY: Bruton’s Tyrosine Kinase (BTK) was originally considered to be primarily expressed in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, elevated expression of novel BTK isoforms of 80 and 65 kDa have been recently described for several solid tumor entities. These newly described isoforms have been linked to tumor growth and poor prognosis. Therefore, we aimed to investigate whether BTK isoforms are also expressed in head and neck squamous cell carcinoma (HNSCC) and further the molecular and cellular consequences of BTK expression for HNSCC tumorigenesis. We confirmed the expression of the BTK-p65 and BTK-p80 isoforms in HNSCC and revealed that both isoforms are products of the same mRNA. Abrogation of BTK activity inhibited tumor progression in our study. Thus, targeting BTK activity appears as a promising therapeutic option for patients suffering from BTK expressing HNSCC. ABSTRACT: Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients. |
format | Online Article Text |
id | pubmed-9818583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98185832023-01-07 BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression Betzler, Annika C. Strobel, Hannah Abou Kors, Tsima Ezić, Jasmin Lesakova, Kristina Pscheid, Ronja Azoitei, Ninel Sporleder, Johanna Staufenberg, Anna-Rebekka Drees, Robert Weissinger, Stephanie E. Greve, Jens Doescher, Johannes Theodoraki, Marie-Nicole Schuler, Patrick J. Laban, Simon Kibe, Toshiro Kishida, Michiko Kishida, Shosei Idel, Christian Hoffmann, Thomas K. Lavitrano, Marialuisa Grassilli, Emanuela Brunner, Cornelia Cancers (Basel) Article SIMPLE SUMMARY: Bruton’s Tyrosine Kinase (BTK) was originally considered to be primarily expressed in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, elevated expression of novel BTK isoforms of 80 and 65 kDa have been recently described for several solid tumor entities. These newly described isoforms have been linked to tumor growth and poor prognosis. Therefore, we aimed to investigate whether BTK isoforms are also expressed in head and neck squamous cell carcinoma (HNSCC) and further the molecular and cellular consequences of BTK expression for HNSCC tumorigenesis. We confirmed the expression of the BTK-p65 and BTK-p80 isoforms in HNSCC and revealed that both isoforms are products of the same mRNA. Abrogation of BTK activity inhibited tumor progression in our study. Thus, targeting BTK activity appears as a promising therapeutic option for patients suffering from BTK expressing HNSCC. ABSTRACT: Here, we describe the expression of Bruton’s Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC) cell lines as well as in primary HNSCC samples. BTK is a kinase initially thought to be expressed exclusively in cells of hematopoietic origin. Apart from the 77 kDa BTK isoform expressed in immune cells, particularly in B cells, we identified the 80 kDa and 65 kDa BTK isoforms in HNSCC, recently described as oncogenic. Importantly, we revealed that both isoforms are products of the same mRNA. By investigating the mechanism regulating oncogenic BTK-p80/p65 expression in HNSSC versus healthy or benign tissues, our data suggests that the epigenetic process of methylation might be responsible for the initiation of BTK-p80/p65 expression in HNSCC. Our findings demonstrate that chemical or genetic abrogation of BTK activity leads to inhibition of tumor progression in terms of proliferation and vascularization in vitro and in vivo. These observations were associated with cell cycle arrest and increased apoptosis and autophagy. Together, these data indicate BTK-p80 and BTK-p65 as novel HNSCC-associated oncogenes. Owing to the fact that abundant BTK expression is a characteristic feature of primary and metastatic HNSCC, targeting BTK activity appears as a promising therapeutic option for HNSCC patients. MDPI 2023-01-03 /pmc/articles/PMC9818583/ /pubmed/36612306 http://dx.doi.org/10.3390/cancers15010310 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 Betzler, Annika C. Strobel, Hannah Abou Kors, Tsima Ezić, Jasmin Lesakova, Kristina Pscheid, Ronja Azoitei, Ninel Sporleder, Johanna Staufenberg, Anna-Rebekka Drees, Robert Weissinger, Stephanie E. Greve, Jens Doescher, Johannes Theodoraki, Marie-Nicole Schuler, Patrick J. Laban, Simon Kibe, Toshiro Kishida, Michiko Kishida, Shosei Idel, Christian Hoffmann, Thomas K. Lavitrano, Marialuisa Grassilli, Emanuela Brunner, Cornelia BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title | BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title_full | BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title_fullStr | BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title_full_unstemmed | BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title_short | BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression |
title_sort | btk isoforms p80 and p65 are expressed in head and neck squamous cell carcinoma (hnscc) and involved in tumor progression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9818583/ https://www.ncbi.nlm.nih.gov/pubmed/36612306 http://dx.doi.org/10.3390/cancers15010310 |
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