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)

Leichtle, Franziska; Betzler, Annika C.; Eizenberger, Carlotta; Lesakova, Kristina; Ezić, Jasmin; Drees, Robert; Greve, Jens; Schuler, Patrick J.; Laban, Simon; Hoffmann, Thomas K.; Cordes, Nils; Lavitrano, Marialuisa; Grassilli, Emanuela; Brunner, Cornelia

doi:10.3390/ijms241713133

Cited by 2 publications

(1 citation statement)

References 54 publications

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“…ATP8B3 (belongs to P4-ATPases) is a subfamily member of P-type ATPases that flip phospholipids across membranes to generate lipid asymmetry, which participate in cell component composition [ 42 ]. BTK encodes Bruton’s Tyrosine Kinase and plays an oncogenic role on head and neck squamous cell carcinoma, promoting epithelial–mesenchymal transition processes and cancer stem cell enrichment [ 43 ]. Research have indicated that Inhibitors targeted to BTK have been developed for hematological tumors [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Song,

Zhao,

Zhao

et al. 2023

Cancer Cell Int

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Lung cancer is the leading cause of cancer-related death. Lysosomes are key degradative compartments that maintain protein homeostasis. In current study, we aimed to construct a lysosomes-related genes signature to predict the overall survival (OS) of patients with Lung Adenocarcinoma (LUAD). Differentially expressed lysosomes-related genes (DELYs) were analyzed using The Cancer Genome Atlas (TCGA-LUAD cohort) database. The prognostic risk signature was identified by Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression and multivariate Cox analysis. The predictive performance of the signature was assessed by Kaplan–Meier curves and Time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the potential molecular biological function and signaling pathways. ESTIMATE and single sample gene set enrichment analysis (ssGSEA) were applied to estimate the difference of tumor microenvironment (TME) between the different risk subtypes. An eight prognostic genes (ACAP3, ATP8B3, BTK, CAV2, CDK5R1, GRIA1, PCSK9, and PLA2G3) signature was identified and divided patients into high-risk and low-risk groups. The prognostic signature was an independent prognostic factor for OS (HR > 1, p < 0.001). The molecular function analysis suggested that the signature was significantly correlated with cancer-associated pathways, including angiogenesis, epithelial mesenchymal transition, mTOR signaling, myc-targets. The low-risk patients had higher immune cell infiltration levels than high-risk group. We also evaluated the response to chemotherapeutic, targeted therapy and immunotherapy in high- and low-risk patients with LUAD. Furthermore, we validated the expression of the eight gene expression in LUAD tissues and cell lines by qRT-PCR. LYSscore signature provide a new modality for the accurate diagnosis and targeted treatment of LUAD and will help expand researchers’ understanding of new prognostic models.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Song,

Zhao,

Zhao

et al. 2023

Cancer Cell Int

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Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell‐Like Properties in Osteosarcoma

Tsai,

Lien,

Wang

et al. 2024

Environmental Toxicology

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Osteosarcoma, a highly aggressive bone cancer, often develops resistance to conventional chemotherapeutics, leading to poor prognosis and survival rates. The malignancy and chemoresistance of osteosarcoma pose significant challenges in its treatment, highlighting the critical need for novel therapeutic approaches. Bruton's tyrosine kinase (BTK) plays a pivotal role in B‐cell development and has been linked to various cancers, including breast, lung, and oral cancers, where it contributes to tumor growth and chemoresistance. Despite its established importance in these malignancies, the impact of BTK on osteosarcoma remains unexplored. Our study delves into the expression levels of BTK in osteosarcoma tissues by data from the GEO and TCGA database, revealing a marked increase in BTK expression compared with primary osteoblasts and a potential correlation with primary site progression. Through our investigations, we identified a subset of osteosarcoma cells, named cis‐HOS, which exhibited resistance to cisplatin. These cells displayed characteristics of cancer stem cells (CSCs), demonstrated a higher angiogenesis effect, and had an increased migration ability. Notably, an upregulation of BTK was observed in these cisplatin‐resistant cells. The application of ibrutinib, a BTK inhibitor, significantly mitigated these aggressive traits. Our study demonstrates that BTK plays a crucial role in conferring chemoresistance in osteosarcoma. The upregulation of BTK in cisplatin‐resistant cells was effectively countered by ibrutinib. These findings underscore the potential of targeting BTK as an effective strategy to overcome chemoresistance in osteosarcoma treatment.

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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)

Cited by 2 publications

References 54 publications

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Identification and validation of eight lysosomes-related genes signatures and correlation with immune cell infiltration in lung adenocarcinoma

Inhibiting Bruton's Tyrosine Kinase to Counteract Chemoresistance and Stem Cell‐Like Properties in Osteosarcoma

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