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G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts

De Francesco, EM; Sotgia, F; Clarke, RB; Lisanti, MP; Maggiolini, M

G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts Thumbnail


Authors

EM De Francesco

RB Clarke

M Maggiolini



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.

Citation

De Francesco, E., Sotgia, F., Clarke, R., Lisanti, M., & Maggiolini, M. (2017). G protein-coupled receptors at the crossroad between physiologic and pathologic angiogenesis : old paradigms and emerging concepts. International Journal of Molecular Sciences, 18(12), https://doi.org/10.3390/ijms18122713

Journal Article Type Article
Acceptance Date Dec 11, 2017
Online Publication Date Dec 14, 2017
Publication Date Dec 14, 2017
Deposit Date Jan 3, 2018
Publicly Available Date Jan 3, 2018
Journal International Journal of Molecular Sciences
Print ISSN 1661-6596
Publisher MDPI
Volume 18
Issue 12
DOI https://doi.org/10.3390/ijms18122713
Keywords GPCR, GPER, HIF-1, SDF-1, VEGF, sphingosine-1P, tumor angiogenesis, tumor microenvironment
Publisher URL http://dx.doi.org/10.3390/ijms18122713
Related Public URLs http://www.mdpi.com/journal/ijms

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