Transcriptomics analysis identified ezrin as a potential druggable target in cervical and gastric cancer cells

Author(s)

Carvalho, Maria Fernanda Lopes ; Calicchio, Carolina Santana ; de Almeida, Bruna Oliveira ; de Miranda, Livia Bassani Lins ; da Silva, Jean Carlos Lipreri ; Lima, Keli ; Machado-Neto, Joao Agostinho

• Document type: Journal article
• Source: Clinics; v. 79, p. 10-pg., 2024-07-06.

Abstract

Objective: 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 identi fied potential cancers that could bene fit from anti- EZR therapies. Methods: 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 identi fied differentially expressed genes. Cell lines were treated with NSC305787, and its effects were assessed through various cellular and molecular assays. Results: 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. Conclusion: The present findings provide promising evidence that ezrin may be a molecular target in the treatment of cervical and gastric carcinoma. (AU)

• FAPESP's process: 20/12842-0 - Impact of genetic ancestry on development, molecular characteristics and clinical outcome in adult patients with Acute Lymphoblastic Leukemia
• Grantee: Keli Cristina de Lima
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/23864-7 - Comprehensive analysis of genomic data for identification and validation of novel therapeutic targets involved in cellular cytoskeleton regulation in acute Leukemia
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 23/12246-6 - Evaluation of the antineoplastic effects of the multikinase inhibitor AD80 in hematologic malignancies with constitutive activation of tyrosine-kinase pathways
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/11038-8 - Investigation of ANKHD1-related signaling pathways and biological processes in Stomach Cancer
• Grantee: Bruna Oliveira de Almeida
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 20/12909-7 - Investigation of the antineoplastic potential of ezrin inhibition in acute Leukemia models
• Grantee: Jean Carlos Lipreri da Silva
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 22/14505-6 - Investigation of the antineoplastic potential of pharmacological inhibition of ezrin in solid tumors: gastric adenocarcinoma and cervical carcinoma
• Grantee: Maria Fernanda Lopes Carvalho
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 21/11606-3 - Investigation of the antineoplastic effects of novel PIP4K2 and HDAC inhibitors in hematologic malignancies
• Grantee: João Agostinho Machado Neto
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03316-8 - Investigation of the effects of the multikinase inhibitor AD80 in hematological neoplasms with constitutive activation of tyrosine kinase pathways
• Grantee: Lívia Bassani Lins de Miranda
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)