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

作者：Andradas Clara; Blasco Benito Sandra; Castillo Lluva Sonia; Dillenburg Pilla Patricia; Diez Alarcia Rebeca; Juanes Garcia Alba; Garcia Taboada Elena; Hernando Llorente Rodrigo; Soriano Joaquim; Hamann Sigrid; Wenners Antonia; Alkatout Ibrahim; Klapper Wolfram; Rocken Christoph; Bauer Maret; Arnold Norbert; Quintanilla Miguel; Megias Diego; Vicente Manzanares Miguel; Uriguen Leyre; Gutkind J Silvio; Guzman Manuel; Perez Gomez Eduardo^*; Sanchez Cristina^*

来源：Oncotarget, 2016, 7(30): 47565-47575.

DOI：10.18632/oncotarget.10206

• GPR55
• G protein-coupled receptor
• cannabinoids
• metastasis
• 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 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 G(q/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.

• 出版日期2016-7-26
• 单位NIH