The role of connexin 43 as a scaffold protein in c-Src pathway in glioblastomas

• Ano de defesa: 2025
• Autor(a) principal: Furtado, Manuela Vilas Carvalho
• Orientador(a): Almeida, Marcelo Cossenza Pettezzoni de
• Banca de defesa: Garcia, Carlos Gustavo , Calaza, Karin da Costa , Carvalho, Roberto Paes de
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Link de acesso: https://app.uff.br/riuff/handle/1/36604
• topic: glioblastoma multiforme; c-Src; connexin 43; tumor progression; therapeutic targets; Glioma, Glioblastoma, Sistema nervoso central, Medicamento; glioblastoma multiforme; c-Src; conexina 43; progressão tumoral; alvos terapêuticos

Gliomas are tumors of the central nervous system (CNS) originating from glial cells, including astrocytes, oligodendrocytes, and ependymal cells. They represent the most prevalent type of primary brain tumor, accounting for about 75% of malignant CNS tumors in adults. The global incidence of gliomas is about 3.4 cases per 100,000 people per year, with a higher prevalence in men. Glioblastoma multiforme (GBM), classified as grade IV glioma by the World Health Organization (WHO), is the most malignant and common primary brain carcinoma, with a survival rate of around 16 months. GBMs are highly aggressive, with rapid proliferation and diffuse infiltration into brain tissue, rendering them difficult to treat with the current treatment regimens combining maximal surgical resection, radiotherapy, and chemotherapy with temozolomide. Despite ongoing efforts to understand the intrinsic mechanisms of these tumors, recurrence and patient death are almost inevitable. The c-Src signaling pathway has emerged as a critical field of study in glioblastomas. c-Src is an oncoprotein that regulates cellular behavior and contributes to tumor progression. Although its role is well stablished, the precise mechanisms by which c-Src influences metabolism and cell transformation remain poorly understood. Connexins are transmembrane proteins that facilitate intercellular communication through gap junctions. Aberrant expression of connexins, such as connexin 43 (Cx43), can affect cancer development and progression, including drug resistance. Cx43 not only forms gap junctions but recent studies showed its ability of also acting as a scaffold to recruit proteins critical for tumor progression, including c-Src. The physical interaction between Cx43 and c-Src may reduce the oncogenic activity of c-Src, but the involved mechanisms and potential therapeutic interventions remain under investigation. This review aims to summarize current knowledge regarding Cx43 expression in glioblastomas and its interaction with c-Src, emphasizing their roles in tumor malignancy and exploring their potential as targets for new therapeutic approaches.