title: Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.
abstract: The orphan G protein-coupled receptor GPR55 has been directly or indirectly related to basic alterations that drive malignant growth: uncontrolled cancer cell proliferation, sustained angiogenesis, and cancer cell adhesion and migration. However, little is known about the involvement of this receptor in metastasis. Here, we show that elevated GPR55 expression in human tumors is associated with the aggressive basal/triple-negative breast cancer population, higher probability to develop metastases, and therefore poor patient prognosis. Activation of GPR55 by its proposed endogenous ligand lysophosphatidylinositol confers pro-invasive features on breast cancer cells both in vitro and in vivo. Specifically, this effect is elicited by coupling to Gq/11 heterotrimeric proteins and the subsequent activation, through ERK, of the transcription factor ETV4/PEA3. Together, these data show that GPR55 promotes breast cancer metastasis, and supports the notion that this orphan receptor may constitute a new therapeutic target and potential biomarker in the highly aggressive triple-negative subtype.
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Clara
authors.initials: C
authors.lastname: Andradas
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Blasco-Benito
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Castillo-Lluva
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Patricia
authors.initials: P
authors.lastname: Dillenburg-Pilla
authors.affiliation: Department of Pharmacology, University of The Basque Country UPV/EHU and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Diez-Alarcia
authors.affiliation: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa and Universidad Autónoma de Madrid, School of Medicine, Madrid, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Juanes-García
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: García-Taboada
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Hernando-Llorente
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Soriano
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hamann
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Antonia
authors.initials: A
authors.lastname: Wenners
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Alkatout
authors.affiliation: Institute of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Institute of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Rocken
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Maret
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Arnold
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Quintanilla
authors.affiliation: Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: Megías
authors.affiliation: Instituto de Investigación Sanitaria Hospital Universitario de la Princesa and Universidad Autónoma de Madrid, School of Medicine, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Vicente-Manzanares
authors.affiliation: Department of Pharmacology, University of The Basque Country UPV/EHU and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
authors.forename: Leyre
authors.initials: L
authors.lastname: Urigüen
authors.affiliation: Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.|Department of Pharmacology, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.|Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Guzmán
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Pérez-Gómez
authors.affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.|Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez
mesh_terms: D017500:Adenovirus E1A Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D005260:Female; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology*; D009362:Neoplasm Metastasis; D011518:Proto-Oncogene Proteins / Q000502:physiology; D050783:Proto-Oncogene Proteins c-ets; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D017500:Adenovirus E1A Proteins; C079853:ETV4 protein, human; C524885:GPR55 protein, human; D008246:Lysophospholipids; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D043882:Receptors, Cannabinoid; D043562:Receptors, G-Protein-Coupled; C025449:lysophosphatidylinositol; D048049:Extracellular Signal-Regulated MAP Kinases; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein
keywords: G protein-coupled receptor; GPR55; cannabinoids; metastasis; triple-negative breast cancer