Context-dependent roles for lymphotoxin-beta receptor signaling in cancer development

• Autor(a) principal: Fernandes, Mónica T.
• Data de Publicação: 2016
• Outros Autores: Dejardin, Emmanuel, Rodrigues Dos Santos, Nuno
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.1/9527

The LT alpha(1)beta(2) and LIGHT TNF superfamily cytokines exert pleiotropic physiological functions through the activation of their cognate lymphotoxin-beta receptor (LT beta R). Interestingly, since the discovery of these proteins, accumulating evidence has pinpointed a role for LT beta R signaling in carcinogenesis. Early studies have shown a potential anti-tumoral role in a subset of solid cancers either by triggering apoptosis in malignant cells or by eliciting an anti-tumor immune response. However, more recent studies provided robust evidence that LT beta R signaling is also involved in diverse cell-intrinsic and microenvironment-dependent pro-oncogenic mechanisms, affecting several solid and hematological malignancies. Consequently, the usefulness of LT beta R signaling axis blockade has been investigated as a potential therapeutic approach for cancer. Considering the seemingly opposite roles of LT beta R signaling in diverse cancer types and their key implications for therapy, we here extensively review the different mechanisms by which LT beta R activation affects carcinogenesis, focusing on the diverse contexts and different models assessed. (C) 2016 Elsevier B.V. All rights reserved.