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Oncotarget. 2016 Jul 26;7(30):47565-47575. doi: 10.18632/oncotarget.10206.

Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.

Author information

1
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
2
Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
3
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
4
Department of Pharmacology, University of The Basque Country UPV/EHU and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
5
Instituto de Investigación Sanitaria Hospital Universitario de la Princesa and Universidad Autónoma de Madrid, School of Medicine, Madrid, Spain.
6
Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
7
Department of Gynecology and Obstetrics, University Hospital Schleswig-Holstein, Kiel, Germany.
8
Institute of Pathology, University Hospital Schleswig-Holstein, Kiel, Germany.
9
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
10
Department of Pharmacology, University of California San Diego, Moores Cancer Center, La Jolla, CA, USA.
11
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain.

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.

KEYWORDS:

G protein-coupled receptor; GPR55; cannabinoids; metastasis; triple-negative breast cancer

PMID:
27340777
PMCID:
PMC5216961
DOI:
10.18632/oncotarget.10206
[Indexed for MEDLINE]
Free PMC Article

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