The biological role of EEF1D, fascin and plectin on oral squamous cell carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) is the eighth most prevalent malignant neoplasm, and accounts for 2% of all deaths by cancer worldwide. OSCCs have a highly variable clinical course, and because it is often diagnosed only after it has reached an advanced stage, the overall survival rate is less than 50% in 5 years. The main prognostic factor for OSCC patients is still the clinical stage of the disease (TNM stage), however, as survival for patients with the same disease stage varies considerably, a better knowledge of the mechanisms that influence its development and progression as well as the characterization of biomarkers related to diagnosis and treatment, is needed. To identify potential biomarkers for OSCC, in collaboration with Dra. Adriana Franco Paes Leme (Laboratório de Espectrometria de Massas, Laboratório Nacional de Biociências, LNBio, CNPEM, Campinas), we have analyzed microdissected epithelia from normal oral mucosa (patients without history of exposure to risk factors related to OSCC such as smoking and alcohol consumption) and from OSCC using liquid chromatography coupled to mass spectrometry. With a false discovery rate (FDR) set at 1%, more than 2500 proteins were identified, and 107 of those had significantly higher expression in OSCC than normal oral mucosa in a ratio >1.5, revealing important pathways such as cell adhesion, cell motility, cell signaling regulated by integrins, cell anchorage and junctional adhesion. Among the proteins with higher levels in OSCC are eukaryotic translation elongation factor 1 delta (EEF1D), fascin and plectin. While EEF1D is related to translation process fascin and pectin are citoeskeletal proteins with both structural and functional activities, including control of cell motility. More important, all 3 proteins show functions related to tumor development and/or progression, and their dysregulated expressions were identified in several tumors, representing good targets to cancer. Thus, the main goal of this study is to understand the biological role of EEF1D, fascin and plectin on oral cancer. After validation, the effects of EEF1D, fascin and plectin on proliferation, apoptosis, adhesion, invasion, epithelial-mesenchymal transition (EMT) and tumor growth formation will be assessed in a small interference system. Immunohistochemical analysis will be performed to determine the prognostic role of EEF1D, fascin and plectin. This project is not designed to understand all aspects of EEF1D, fascin and plectin on oral cancer, however, assuming that their functions are related to cancer development and progression, a profound knowledge is important to use EEF1D, fascin and plectin as biomarkers of the oral cancer. (AU)