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Int. J. Mol. Sci. 2017, 18(12), 2713; https://doi.org/10.3390/ijms18122713

G Protein-Coupled Receptors at the Crossroad between Physiologic and Pathologic Angiogenesis: Old Paradigms and Emerging Concepts

1
Department of Pharmacy, Health and Nutrition Sciences, University of Calabria via Savinio, 87036 Rende, Italy
2
Breast Cancer Now Research Unit, Division of Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester M20 4GJ, UK
3
Translational Medicine, School of Environment and Life Sciences, Biomedical Research Centre, University of Salford, Greater Manchester M5 4WT, UK
*
Author to whom correspondence should be addressed.
Received: 30 October 2017 / Revised: 11 December 2017 / Accepted: 11 December 2017 / Published: 14 December 2017
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract

G protein-coupled receptors (GPCRs) have been implicated in transmitting signals across the extra- and intra-cellular compartments, thus allowing environmental stimuli to elicit critical biological responses. As GPCRs can be activated by an extensive range of factors including hormones, neurotransmitters, phospholipids and other stimuli, their involvement in a plethora of physiological functions is not surprising. Aberrant GPCR signaling has been regarded as a major contributor to diverse pathologic conditions, such as inflammatory, cardiovascular and neoplastic diseases. In this regard, solid tumors have been demonstrated to activate an angiogenic program that relies on GPCR action to support cancer growth and metastatic dissemination. Therefore, the manipulation of aberrant GPCR signaling could represent a promising target in anticancer therapy. Here, we highlight the GPCR-mediated angiogenic function focusing on the molecular mechanisms and transduction effectors driving the patho-physiological vasculogenesis. Specifically, we describe evidence for the role of heptahelic receptors and associated G proteins in promoting angiogenic responses in pathologic conditions, especially tumor angiogenesis and progression. Likewise, we discuss opportunities to manipulate aberrant GPCR-mediated angiogenic signaling for therapeutic benefit using innovative GPCR-targeted and patient-tailored pharmacological strategies. View Full-Text
Keywords: GPCR; tumor angiogenesis; tumor microenvironment; VEGF; HIF-1; GPER; SDF-1; sphingosine-1P GPCR; tumor angiogenesis; tumor microenvironment; VEGF; HIF-1; GPER; SDF-1; sphingosine-1P
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De Francesco, E.M.; Sotgia, F.; Clarke, R.B.; Lisanti, M.P.; Maggiolini, M. G Protein-Coupled Receptors at the Crossroad between Physiologic and Pathologic Angiogenesis: Old Paradigms and Emerging Concepts. Int. J. Mol. Sci. 2017, 18, 2713.

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