Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling

Estefanía Moreno, Clara Andradas, Mireia Medrano, María M. Caffarel, Eduardo Perez-Gomez, Sandra Blasco-Benito, Maria Gomez-Canas, M. Ruth Pazos, Andrew J. Irving, Carme Lluis, Enric I. Canela, Javier Fernandez-Ruiz, Manuel Guzmán, P. J. McCormick, Cristina Sanchez

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)21960-21972
Number of pages13
JournalThe Journal of Biological Chemistry
Volume289
Issue number32
Early online date18 Jun 2014
DOIs
Publication statusPublished - 8 Aug 2014

Keywords

  • cancer
  • Cannabinoid
  • Cannabinoid Receptor
  • G Protein-coupled Receptor (GPCR)
  • Signal Transduction

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