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Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling
Authors:Estefanía Moreno  Clara Andradas  Mireia Medrano  María M. Caffarel  Eduardo Pérez-Gómez  Sandra Blasco-Benito  María Gómez-Ca?as  M. Ruth Pazos  Andrew J. Irving  Carme Lluís  Enric I. Canela  Javier Fernández-Ruiz  Manuel Guzmán  Peter J. McCormick  Cristina Sánchez
Abstract:The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology.
Keywords:Cancer   Cannabinoid   Cannabinoid Receptor   G Protein-coupled Receptor (GPCR)   Signal Transduction
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