BTK Isoforms p80 and p65 Are Expressed in Head and Neck Squamous Cell Carcinoma (HNSCC) and Involved in Tumor Progression.

Autor: Betzler AC; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Strobel H; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Abou Kors T; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Ezić J; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Lesakova K; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Pscheid R; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Azoitei N; Department of Internal Medicine I, Ulm University Medical Center, 89081 Ulm, Germany., Sporleder J; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Staufenberg AR; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Drees R; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Weissinger SE; Institute of Pathology, Ulm University Medical Center, 89081 Ulm, Germany., Greve J; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Doescher J; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Theodoraki MN; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Schuler PJ; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Laban S; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Kibe T; Department of Biochemistry and Genetics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8580, Japan., Kishida M; Department of Biochemistry and Genetics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8580, Japan., Kishida S; Department of Biochemistry and Genetics, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8580, Japan., Idel C; Department of Otorhinolaryngology, University Hospital Schleswig-Holstein, University of Luebeck, Campus Luebeck, 23538 Luebeck, Germany., Hoffmann TK; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany., Lavitrano M; School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy., Grassilli E; School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy., Brunner C; Department of Oto-Rhino-Laryngology, Ulm University Medical Center, 89075 Ulm, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2023 Jan 03; Vol. 15 (1). Date of Electronic Publication: 2023 Jan 03.
DOI: 10.3390/cancers15010310
Abstrakt: 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.
Databáze: MEDLINE
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