Structural proteomics for the search of therapeutic targets in oral cancer

• Grant number: 22/14348-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: April 01, 2023
• Status: Discontinued
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Adriana Franco Paes Leme
• Grantee: Guilherme Araújo Câmara
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia e Inovação (Brasil). Campinas , SP, Brazil
• Associated research grant: 18/18496-6 - The role of alcohol treated-extracellular vesicles in oral cells transformation, AP.TEM
• Associated scholarship(s): 25/00104-8 - Exploring expansion proteomics to evaluate protein-protein interactions, BE.EP.DR

Abstract

Treatment of patients with oral squamous cell carcinoma (OSCC) represents a clinical challenge. Despite advances in therapeutic modalities, OSCC recurrence rates vary between 18% to 76% in patients that received the standard treatment of surgery, radiotherapy and/or chemotherapy. Moreover, OSCC patients demonstrates a low response to other therapeutic modalities, such as EGFR monotherapy and immunotherapy. In a previous study (Carnielli et al., 2018), our group revealed an association of CSTB, NDRG1 and PGK1 with OSCC prognosis, suggesting the hypothesis that these proteins may be involved in OSCC progression. Therefore, we propose the application of orthogonal structural proteomics strategies for the characterization of the interactome of these proteins, in order to reveal their potential roles in OSCC progression. For that, the characterization of these differential interactomes will be evaluated in normal (HMK) and transformed (SCC-25 and HSC3) keratinocytes. The strategies to be employed for the characterization of these differential interactomes are proximity-dependent biotinylation and co-fractionation. Furthermore, crosslinkers will be employed for the tridimensional characterization of interaction interfaces. This set of methods will allow to prioritize the protein complexes to be modulated by peptides designed against their interaction interfaces and the effect of this modulation will be evaluated by functional assays. Lastly, limited proteolysis will be employed for the evaluation of structural changes in protein complexes after peptide treatment, predicting the effects of this treatment on the whole proteome.