Molecular Mechanisms Deployed by Virally Encoded G Protein–Coupled Receptors in Human Diseases

Montaner, Silvia; Kufareva, Irina; Abagyan, Ruben; Gutkind, J. Silvio

doi:10.1146/annurev-pharmtox-010510-100608

Cited by 52 publications

(51 citation statements)

References 135 publications

(157 reference statements)

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“…Additionally, CXCL8-CXCR2 signaling facilitates migration and proliferation of endothelial cells [92] , and the AKT pathway is important for GPCR-dependent angiogenesis [93] following CXCR1 and CXCR2 activation [49,81] . Also, the human herpesvirus-8, an etiological agent of the highly vascular Kaposi's sarcoma, induces expression of CXCL8 [94] , providing further evidence for chemokine involvement in tumorigenesis [95] .…”

Section: Chemokines and Angiogenesismentioning

confidence: 97%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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Core tip: The chemokine network makes an attractive target for therapeutic intervention in many tumor types, including those of the gastrointestinal tract. However, we need to define more selective and specific targets, to minimize systemic side effects during treatment. INTRODUCTION Cancer development and progression in the gastrointestinal tractCancer is a disease in which normal cells acquire genetic and epigenetic abnormalities [1,2] , leading to disorientation of conventional processes for the maintenance of normal cell physiology. These aberrant genetic and epigenetic modifications to the normal cell induce abnormal cell motility, proliferation, and survival, eventually enabling these cells to invade into adjacent tissues and even to migrate to regional or distant organs where they may grow continuously as metastatic lesions [3] . For many cancer patients, metastasis is generally the major cause of disease-related death [4,5] . Therefore, it is indispensable to elucidate the basic molecular mechanisms of tumor development to identify effective therapeutic targets, which can possibly reduce the side-effects of treatment, and define useful molecular markers for early detection and prediction of disease course. Especially, the newly emerged concept of personalized medicine may require in-depth assessment of potential therapeutic molecular target(s) in each individual case through analysis of sig- REVIEW Chemokines, chemokine receptors and the gastrointestinal system AbstractThe biological properties of tumor cells are known to be regulated by a multitude of cytokines and growth factors, which include epidermal growth factor receptor agonists and members of the transforming growth factor β family. Furthermore, the recent explosion of research in the field of chemokine function as mediators of tumor progression has led to the possibility that these small, immunomodulatory proteins also play key roles in carcinogenesis and may, therefore, be potential targets for novel therapeutic approaches. In this review, we will summarize recently reported findings in chemokine biology with a focus on the gastrointestinal tract.

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Section: Chemokines and Angiogenesismentioning

confidence: 97%

Chemokines, chemokine receptors and the gastrointestinal system

Miyazaki¹,

Takabe²,

Yeudall³

2013

WJG

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“…At least seven human viruses, Epstein-Barr virus (EBV/HHV- 4), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), human T-cell lymphotropic virus (HTLV-1), and Kaposi's associated sarcoma herpes virus (KSHV/HHV- 8), and Merkel cell polyomavirus, contribute to 10-15% of cancers [48,49]. Surprisingly, many human viruses harbor open reading frames encoding GPCRs in their viral genomes, indicating that these signaling circuits are required for replicative success [50]. For example, EBV encodes one GPCR (BILF1), and human cytomegalovirus (HCMV/HHV-5) expresses at least four GPCRs (US28, US27, UL33 and UL78).…”

Section: Viral Gpcrsmentioning

confidence: 99%

Novel insights into G protein and G protein-coupled receptor signaling in cancer

O’Hayre

Degese

Gutkind

2014

Current Opinion in Cell Biology

242

213

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G protein-coupled receptors (GPCRs) play a central role in signal transmission, thereby controlling many facets of cellular function. Overwhelming evidence now implicates GPCRs, G proteins and their downstream signaling targets in cancer initiation and progression, where they can influence aberrant cell growth and survival, largely through activation of AKT/mTOR, MAPKs, and Hippo signaling pathways. GPCRs also play critical roles in the invasion and metastasis of cancer cells via activation of Rho GTPases and cytoskeletal changes, and angiogenesis to supply the tumor with nutrients and provide routes for metastasis. Lastly, GPCRs contribute to the establishment and maintenance of a permissive tumor microenvironment. Understanding GPCR involvement in cancer malignancy may help identify novel therapeutic opportunities for cancer prevention and treatment.

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“…While IL-10 is a highly conserved target, nearly every aspect of the chemokine system has been exploited by viral pathogens [16–19]. Manipulation of chemokine signaling networks can aid in virus dissemination, modulate host cell trafficking to inhibit immune clearance, or alter intracellular signaling to promote a favorable environment for virus replication (Figure 3).…”

Section: Other Inflammatory Mediators: Chemokine Signalingmentioning

confidence: 99%

“…Besides KHSV, many viruses encode proteins with homology to chemokines and chemokine receptors [19,27]. The G protein of respiratory syncytial virus (RSV) contains a CX3C motif that mediates binding to cells expressing CX3CR1, reducing inflammatory cytokines and resulting in impaired innate and adaptive immune responses [28].…”

Section: Other Inflammatory Mediators: Chemokine Signalingmentioning

confidence: 99%

Viral manipulation of the host immune response

Christiaansen

Varga

Spencer

2015

Current Opinion in Immunology

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Viruses are obligate intracellular parasites that require a host for essential machinery to replicate and ultimately be transmitted to new susceptible hosts. At the same time, the immune system has evolved to protect the human body from invasion by viruses and other pathogens. To counter this, viruses have developed an arsenal of strategies to not only avoid immune detection but to actively manipulate host immune responses to create an environment more favorable for infection. Here, we describe recent advances uncovering novel mechanisms by which viruses skew host immune responses through modulation of cytokine and chemokine signaling networks, interference with antigen presentation and T cell responses, and preventing antibody production.

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Molecular Mechanisms Deployed by Virally Encoded G Protein–Coupled Receptors in Human Diseases

Cited by 52 publications

References 135 publications

Chemokines, chemokine receptors and the gastrointestinal system

Chemokines, chemokine receptors and the gastrointestinal system

Novel insights into G protein and G protein-coupled receptor signaling in cancer

Viral manipulation of the host immune response

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