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J Biol Chem. 2014 Aug 8;289(32):21960-72. doi: 10.1074/jbc.M114.561761. Epub 2014 Jun 18.

Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling.

Author information

1
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.
2
the Department of Biochemistry and Molecular Biology I, School of Biology and the Instituto de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain.
3
the Department of Biochemistry and Molecular Biology I, School of Biology and.
4
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.
5
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.
6
the Division of Neuroscience, Ninewells Hospital, University of Dundee, Dundee DD1 9SY, United Kingdom, and.
7
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.
8
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.
9
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.

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

PMID:
24942731
PMCID:
PMC4139213
DOI:
10.1074/jbc.M114.561761
[Indexed for MEDLINE]
Free PMC Article

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