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

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• 作者：Mó ; nica T. Fernandes^a ; ^b ; Emmanuel Dejardin^c ; Nuno R. dos Santos^a ; ^d ; ^e ; ^{nrsantos@ualg.pt" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Lymphotoxin-β receptor ; Cell signaling ; Lymphotoxin ; LIGHT ; Oncogenesis ; Tumor microenvironment
• 刊名：Biochimica et Biophysica Acta (BBA)-Reviews on Cancer
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：1865
• 期：2
• 页码：204-219
• 全文大小：1646 K

文摘

The LTα₁β₂ and LIGHT TNF superfamily cytokines exert pleiotropic physiological functions through the activation of their cognate lymphotoxin-β receptor (LTβR). Interestingly, since the discovery of these proteins, accumulating evidence has pinpointed a role for LTβR 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 LTβR signaling is also involved in diverse cell-intrinsic and microenvironment-dependent pro-oncogenic mechanisms, affecting several solid and hematological malignancies. Consequently, the usefulness of LTβR signaling axis blockade has been investigated as a potential therapeutic approach for cancer. Considering the seemingly opposite roles of LTβR signaling in diverse cancer types and their key implications for therapy, we here extensively review the different mechanisms by which LTβR activation affects carcinogenesis, focusing on the diverse contexts and different models assessed.