Clara Andradas, Sandra Blasco-Benito, Sonia Castillo-Lluva, Patricia Dillenburg-Pilla, Rebeca Diez-Alarcia, Alba Juanes-García, Elena García-Taboada, Rodrigo Hernando-Llorente, Joaquim Soriano, Sigrid Hamann, Antonia Wenners, Ibrahim Alkatout, Wolfram Klapper, Christoph Rocken, Maret Bauer, Norbert Arnold, Miguel Quintanilla, Diego Megías, Miguel Vicente-Manzanares, Leyre Urigüen, J. Silvio Gutkind, Manuel Guzmán, Eduardo Pérez-Gómez, Cristina Sánchez
Published in Oncotarget
26 July 2016
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.
Andradas C, Blasco-Benito S, Castillo-Lluva S, et al. Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. Oncotarget. 2016;7(30):47565-47575. doi:10.18632/oncotarget.10206