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

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 recepto...

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Detalles Bibliográficos
Autores: Andradas, Clara, Blasco-Benito, Sandra, Castillo-Lluva, Sonia, Dillenburg-Pilla, Patricia, Diez-Alarcia, Rebeca, Juanes-García, Alba, García-Taboada, Elena, Hernando-Llorente, Rodrigo, Soriano, Joaquim, Hamann, Sigrid, Wenners, Antonia, Alkatout, Ibrahim, Klapper, Wolfram, Rocken, Christoph, Bauer, Maret, Arnold, Norbert, Quintanilla, Miguel, Megías, Diego, Vicente-Manzanares, Miguel, Urigüen, Leyre, Gutkind, J Silvio, Guzmán, Manuel, Pérez-Gómez, Eduardo, Sánchez, Cristina
Tipo de recurso: artículo
Fecha de publicación:2016
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/25316
Acceso en línea:https://hdl.handle.net/20.500.12105/25316
Access Level:acceso abierto
Palabra clave:G protein-coupled receptor
GPR55
cannabinoids
metastasis
triple-negative breast cancer
Descripción
Sumario: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.

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