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Publication
Context-dependent roles for lymphotoxin-beta receptor signaling in cancer development
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Advisor(s)
Abstract(s)
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.