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

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