title: Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling.
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.
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Estefanía
authors.initials: E
authors.lastname: Moreno
authors.affiliation: the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Andradas
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Medrano
authors.affiliation: the Department of Biochemistry and Molecular Biology I, School of Biology and.
authors.forename: María M
authors.initials: MM
authors.lastname: Caffarel
authors.affiliation: the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez-Gómez
authors.affiliation: the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blasco-Benito
authors.affiliation: the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, Department of Biochemistry and Molecular Biology III/Instituto Universitario de Investigación en Neuroquímica, School of Medicine, Complutense University, 28040 Madrid, Spain, the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid 28034, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Gómez-Cañas
authors.affiliation: the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, Department of Biochemistry and Molecular Biology III/Instituto Universitario de Investigación en Neuroquímica, School of Medicine, Complutense University, 28040 Madrid, Spain.
authors.forename: M Ruth
authors.initials: MR
authors.lastname: Pazos
authors.affiliation: the Division of Neuroscience, Ninewells Hospital, University of Dundee, Dundee DD1 9SY, United Kingdom, and.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Irving
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Lluís
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain.
authors.forename: Enric I
authors.initials: EI
authors.lastname: Canela
authors.affiliation: the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, Department of Biochemistry and Molecular Biology III/Instituto Universitario de Investigación en Neuroquímica, School of Medicine, Complutense University, 28040 Madrid, Spain, the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid 28034, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Fernández-Ruiz
authors.affiliation: the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid 28034, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Guzmán
authors.affiliation: From the Department of Biochemistry and Molecular Biology, University of Barcelona, 08028 Barcelona, Spain, the Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), 28031 Madrid, Spain, the Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain, the School of Pharmacy, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom p.mccormick@uea.ac.uk.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
authors.affiliation: the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain, cristina.sanchez@quim.ucm.es.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002186:Cannabinoids / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D013759:Dronabinol / Q000494:pharmacology; D005260:Female; D018390:Gene Targeting; D005909:Glioblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D034741:RNA, Small Interfering / Q000235:genetics; D043885:Receptor, Cannabinoid, CB2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: C588309:CNR2 protein, human; D002186:Cannabinoids; C524885:GPR55 protein, human; D034741:RNA, Small Interfering; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D013759:Dronabinol
keywords: Cancer; Cannabinoid; Cannabinoid Receptor; G Protein-coupled Receptor (GPCR); Signal Transduction