Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling

Estefanía Moreno, Clara Andradas, Mireia Medrano, María M. Caffarel, Eduardo Pérez-Gómez, Sandra Blasco-Benito, María Gómez-Cañas, M. Ruth Pazos, Andrew J. Irving, Carme Lluís, Enric I. Canela, Javier Fernández-Ruiz, Manuel Guzmán, Peter J. McCormick (Lead / Corresponding author), Cristina Sánchez (Lead / Corresponding author)

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    Abstract

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. As 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.

    Original languageEnglish
    Pages (from-to)21960-21972
    Number of pages12
    JournalJournal of Biological Chemistry
    Volume289
    Issue number32
    DOIs
    Publication statusPublished - 8 Aug 2014

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    Moreno, E., Andradas, C., Medrano, M., Caffarel, M. M., Pérez-Gómez, E., Blasco-Benito, S., Gómez-Cañas, M., Pazos, M. R., Irving, A. J., Lluís, C., Canela, E. I., Fernández-Ruiz, J., Guzmán, M., McCormick, P. J., & Sánchez, C. (2014). Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling. Journal of Biological Chemistry, 289(32), 21960-21972. https://doi.org/10.1074/jbc.M114.561761