title: Context-dependent roles for lymphotoxin-β receptor signaling in cancer development.
abstract: 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.
authors.affiliation: Centre for Biomedical Research (CBMR), University of Algarve, Faro 8005-139, Portugal; PhD Program in Biomedical Sciences, Department of Biomedical Sciences and Medicine, University of Algarve, Faro 8005-139, Portugal.
authors.forename: Mónica T
authors.initials: MT
authors.lastname: Fernandes
authors.affiliation: Laboratory of Molecular Immunology and Signal Transduction, GIGA-Research, Molecular Biology of Diseases, University of Liège, Liège 4000, Belgium.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dejardin
authors.affiliation: Centre for Biomedical Research (CBMR), University of Algarve, Faro 8005-139, Portugal; Instituto de Investigação e Inovação em Saúde (I3S), Universidade do Porto, Porto 4200, Portugal; Institute of Pathology and Molecular Immunology, University of Porto (IPATIMUP), Porto 4200, Portugal. Electronic address: nrsantos@ualg.pt.
authors.forename: Nuno R
authors.initials: NR
authors.lastname: dos Santos
mesh_terms: D000818:Animals; D006801:Humans; D007249:Inflammation / Q000209:etiology; D053259:Lymphotoxin beta Receptor / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009369:Neoplasms / Q000209:etiology*; D015398:Signal Transduction / Q000502:physiology*; D059016:Tumor Microenvironment; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000502:physiology
chemical_list: D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14
keywords: Cell signaling; LIGHT; Lymphotoxin; Lymphotoxin-β receptor; Oncogenesis; Tumor microenvironment