Influence of Bruton's Tyrosine Kinase (BTK) on Epithelial-Mesenchymal Transition (EMT) Processes and Cancer Stem Cell (CSC) Enrichment in Head and Neck Squamous Cell Carcinoma (HNSCC)
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
Abstract
Constitutively active kinases play a crucial role in carcinogenesis, and their inhibition is a common target for molecular tumor therapy. We recently discovered the expression of two oncogenic isoforms of Bruton's Tyrosine Kinase (BTK) in head and neck squamous cell carcinoma (HNSCC), Btk-p80 and BTK-p65. However, the precise role of BTK in HNSCC remains unclear. Analyses of a tissue microarray containing benign and malignant as well as inflammatory tissue samples of the head and neck region revealed the preferential expression of BTK-p80 in malignant tissue, whereas BTK-p65 expression was confirmed in over 80% of analyzed metastatic head and neck tumor cases. Therefore, processes associated with metastasis, like cancer stem cell (CSC) enrichment and the epithelial-mesenchymal transition (EMT), which in turn depend on an appropriate cytokine milieu, were analyzed. Treatment of HNSCC-derived cell lines cultured under 3D conditions with the BTK inhibitor AVL-292 caused reduced sphere formation, which was accompanied by reduced numbers of ALDH1A1+ CSCs as well as biological changes associated with the EMT. Moreover, we observed reduced NF-κB expression as well as altered NF-κB dependent pro-tumorigenic and EMT-associated cytokine release of IL-6, IFNγ, and TNFα when BTK activity was dampened. Therefore, an autocrine regulation of the oncogenic BTK-dependent process in HNSCC can be suggested, with BTK inhibition expected to be an effective treatment option for HNSCC.
Details
Originalsprache | Englisch |
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Aufsatznummer | 13133 |
Fachzeitschrift | International journal of molecular sciences |
Jahrgang | 24 |
Ausgabenummer | 17 |
Publikationsstatus | Veröffentlicht - 23 Aug. 2023 |
Peer-Review-Status | Ja |
Externe IDs
PubMedCentral | PMC10487612 |
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Scopus | 85170210697 |
ORCID | /0000-0001-5684-629X/work/146646161 |
WOS | 001061918500001 |
Mendeley | c7e6d6c2-a7cf-377e-a13e-f0ff35a92e42 |
Schlagworte
Forschungsprofillinien der TU Dresden
DFG-Fachsystematik nach Fachkollegium
Ziele für nachhaltige Entwicklung
ASJC Scopus Sachgebiete
Schlagwörter
- Humans, Agammaglobulinaemia Tyrosine Kinase, Carcinogenesis, Cytokines, Epithelial-Mesenchymal Transition, Head and Neck Neoplasms/genetics, Neoplastic Stem Cells, NF-kappa B, Squamous Cell Carcinoma of Head and Neck, Hnscc, Emt, Csc, Btk