Viral G protein-coupled receptors as modulators of cancer hallmarks. (June 2020)

• Record Type: Journal Article
• Authors: van Senten, Jeffrey R.; Fan, Tian Shu; Siderius, Marco; Smit, Martine J.
• Is Part Of: Pharmacological research. Volume 156(2020)
• Publication Date: 2020-06
• Subjects: AIDS acquired immunodeficiency syndrome -- AKT protein kinase B -- Ang2 angiopoietin-2 -- AP-1 activator protein-1 -- ARE antioxidant response element -- CAMKII Ca2+/calmodulin-dependent protein kinase II -- CDK2 cyclin-dependent kinase 2 -- COX2 cyclo-oxygenase-2 -- CRE cyclic AMP response element -- CREB cAMP response element-binding protein -- EBNA Epstein-Barr virus nuclear antigen -- EBV Epstein-Barr virus -- ECM extracellular matrix -- EGF endothelial growth factor -- ERK extracellular signal-regulated kinases -- FGF fibroblast growth factor -- GAPDH glyceraldehyde 3-phosphatase dehydrogenase -- gH glycoprotein H -- GPCR G protein-coupled receptor -- HEK293 human embryonic kidney 293 -- HHV human herpesvirus -- HIF hypoxia inducible factor -- HLA human leukocyte antigen -- HO-1 heme oxygenase-1 -- HCMV human cytomegalovirus -- HSV human simplex virus -- HUVEC human umbilical cord vein endothelial cells -- IGF-1 insulin-growth like receptor -- IL interleukin -- JAK janus kinase -- KS Kaposi's sarcoma -- KSHV Kaposi's sarcoma-associatedherpesvirus -- LANA latency-associated nuclear antigen -- MAP mitogen-activated protein -- MAPK mitogen-activated protein kinases -- miR-34 micoRNA-34 -- MCS multicentric Castleman's disease -- MMP matrix metalloproteinases -- mTOR mammalian target of rapamycin -- NFAT nuclear factor of activated T-cells -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- IKK NF-kappa-B inhibitor kinase -- NRF-1 nuclear respiratory factor 1 -- InsP inositol phosphate -- IP3 inositol triphosphate -- ORF74 open reading frame -- PEL primary effusion lymphoma -- PGE2 prostaglandin E2 -- PI3K phosphoinositide 3-kinase -- PKC protein kinase C -- PKM2 pyruvate kinase M2 -- PLC phospholipase C -- PPP pentose phosphate pathway -- RGS4 regulator of G protein signaling 4 -- ROCK Rho-associated protein kinase -- RTK receptor tyrosine kinase -- SERCA2 sarcoplasmic reticulum calcium ATPase 2 -- SESN sestrin-2 -- STAT signal transducer and activator of transcription -- SWAP70 switch-associated protein 70 -- TCA tricarboxylic acid cycle -- TCF/LEF T-cell factor/lymphoid enhancer factor -- TNF tumor necrosis factor -- VEGF vascular endothelial growth factor -- vFLIP viral FLICE-like inhibitory protein; Rapamycin (PubChem CID:5284616) -- cAMP (PubChem CID:6076) -- Celecoxib (PubChem CID: 2662) -- Cyclosporin A (PubChem CID: 5280754) -- Edelfosine (PubChem CID: 1392) -- 2-APB (PubChem CID: 1598) -- Verteporfin (PubChem CID: 5362420); Cytomegalovirus (CMV) -- Kaposi sarcoma virus (KSHV) -- Epstein-Barr virus (EBV) -- Oncomodulation -- Constitutive activity -- Signal transduction; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2020.104804
• Languages: English
• ISSNs: 1043-6618

Abstract

Graphical abstract: Abstract: Herpesviruses encode transmembrane G protein-coupled receptors (GPCRs), which share structural homology to human chemokine receptors. These viral GPCRs include KSHV-encoded ORF74, EBV-encoded BILF1, and HCMV-encoded US28, UL33, UL78 and US27. Viral GPCRs hijack various signaling pathways and cellular networks, including pathways involved in the so-called cancer hallmarks as defined by Hanahan and Weinberg. These hallmarks describe cellular characteristics crucial for transformation and tumor progression. The cancer hallmarks involve growth factor-independent proliferation, angiogenesis, avoidance of apoptosis, invasion and metastasis, metabolic reprogramming, genetic instability and immune evasion amongst others. The role of beta herpesviruses modulating these cancer hallmarks is clearly highlighted by the proliferative and pro-angiogenic phenotype associated with KSHV infection which is largely ascribed to the ORF74-mediated modulation of signaling networks in host cells. For HCMV and Epstein-Bar encoded GPCRs, oncomodulatory effects have been described which contribute to the cancer hallmarks, thereby enhancing oncogenic development. In this review, we describe the main signaling pathways controlling the hallmarks of cancer which are affected by the betaherpesvirus encoded GPCRs. Most prominent among these involve the JAK-STAT, PI(3)K-AKT, NFkB and MAPK signaling nodes. These insights are important to effectively target these viral GPCRs and their signaling networks in betaherpesvirus-associated malignancies.