埃兹林
癌症研究
生物
癌症
癌变
CD44细胞
转录组
宫颈癌
细胞
基因表达
基因
遗传学
细胞骨架
作者
Maria Fernanda Lopes Carvalho,Carolina Santana Calicchio,Bruna Oliveira de Almeida,Lívia Bassani Lins de Miranda,Jean Carlos Lipreri da Silva,Keli Lima,João Agostinho Machado‐Neto
出处
期刊:Clinics
[Fundacao Faculdade de Medicina]
日期:2024-01-01
卷期号:79: 100422-100422
标识
DOI:10.1016/j.clinsp.2024.100422
摘要
Cancer genomics and transcriptomics studies have provided a large volume of data that enables to test of hypotheses based on real data from cancer patients. Ezrin (encoded by the EZR gene) is a highly expressed protein in cancer that contributes to linking the actin cytoskeleton to the cell membrane and signal transduction pathways involved in oncogenesis and disease progression. NSC305787 is a pharmacological ezrin inhibitor with potential antineoplastic effects. In the present study, the authors prospected EZR mRNA levels in a pan-cancer analysis and identified potential cancers that could benefit from anti-EZR therapies. This study analyzed TCGA data for 32 cancer types, emphasizing cervical squamous cell carcinoma and stomach adenocarcinoma. It investigated the impact of EZR transcript levels on clinical outcomes and identified differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. EZR mRNA levels are highly expressed, and their expression is associated with biologically relevant molecular processes in cervical squamous carcinoma and stomach adenocarcinoma. In cellular models of cervical and gastric cancer, NSC305787 reduces cell viability and clonal growth (p < 0.05). Molecular analyses indicate that the pharmacological inhibition of EZR induces molecular markers of cell death and DNA damage, in addition, to promoting the expression of genes associated with apoptosis and inhibiting the expression of genes related to survival and proliferation. The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.
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