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; Cristina Sánchez

doi:10.1074/jbc.M114.561761

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)

Research output: Contribution to journal › Article › peer-review

89 Citations (Scopus)

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 language	English
Pages (from-to)	21960-21972
Number of pages	12
Journal	Journal of Biological Chemistry
Volume	289
Issue number	32
DOIs	https://doi.org/10.1074/jbc.M114.561761
Publication status	Published - 8 Aug 2014

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10.1074/jbc.M114.561761

http://www.jbc.org/content/289/32/21960

Cite this

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

@article{82337bca58164ccab62d436e8223feec,

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. 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.",

author = "Estefan{\'i}a Moreno and Clara Andradas and Mireia Medrano and Caffarel, {Mar{\'i}a M.} and Eduardo P{\'e}rez-G{\'o}mez and Sandra Blasco-Benito and Mar{\'i}a G{\'o}mez-Ca{\~n}as and Pazos, {M. Ruth} and Irving, {Andrew J.} and Carme Llu{\'i}s and Canela, {Enric I.} and Javier Fern{\'a}ndez-Ruiz and Manuel Guzm{\'a}n and McCormick, {Peter J.} and Cristina S{\'a}nchez",

note = "Copyright {\textcopyright} 2014, The American Society for Biochemistry and Molecular Biology.",

year = "2014",

month = aug,

day = "8",

doi = "10.1074/jbc.M114.561761",

language = "English",

volume = "289",

pages = "21960--21972",

journal = "Journal of Biological Chemistry",

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publisher = "American Society for Biochemistry and Molecular Biology",

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Moreno, E, Andradas, C, Medrano, M, Caffarel, MM, Pérez-Gómez, E, Blasco-Benito, S, Gómez-Cañas, M, Pazos, MR, Irving, AJ, Lluís, C, Canela, EI, Fernández-Ruiz, J, Guzmán, M, McCormick, PJ & Sánchez, C 2014, 'Targeting CB₂-GPR55 receptor heteromers modulates cancer cell signaling', Journal of Biological Chemistry, vol. 289, no. 32, pp. 21960-21972. https://doi.org/10.1074/jbc.M114.561761

TY - JOUR

T1 - Targeting CB2-GPR55 receptor heteromers modulates cancer cell signaling

AU - Moreno, Estefanía

AU - Andradas, Clara

AU - Medrano, Mireia

AU - Caffarel, María M.

AU - Pérez-Gómez, Eduardo

AU - Blasco-Benito, Sandra

AU - Gómez-Cañas, María

AU - Pazos, M. Ruth

AU - Irving, Andrew J.

AU - Lluís, Carme

AU - Canela, Enric I.

AU - Fernández-Ruiz, Javier

AU - Guzmán, Manuel

AU - McCormick, Peter J.

AU - Sánchez, Cristina

PY - 2014/8/8

Y1 - 2014/8/8

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AB - 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.

U2 - 10.1074/jbc.M114.561761

DO - 10.1074/jbc.M114.561761

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