• Maria Fernanda Lopes Carvalho, Carolina Santana Calicchio, Bruna Oliveira de Almeida, Livia Bassani Lins de Miranda, Jean Carlos Lipreri da Silva, Keli Lima, and João Agostinho Machado-Neto.
• Department of Pharmacology, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil.
• Clinics (Sao Paulo). 2024 Jan 1; 79: 100422100422.

ObjectiveCancer 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.MethodsThis 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.ResultsEZR 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.ConclusionThe present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma.Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.

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