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

被引：40

作者：

Andradas, Clara ^{[1
,2
]}

Blasco-Benito, Sandra ^{[1
,2
]}

Castillo-Lluva, Sonia ^{[1
]}

Dillenburg-Pilla, Patricia ^{[3
]}

Diez-Alarcia, Rebeca ^{[4
,5
]}

Juanes-Garcia, Alba ^{[6
,7
]}

Garcia-Taboada, Elena ^{[1
]}

Hernando-Llorente, Rodrigo ^{[1
]}

Soriano, Joaquim ^{[8
]}

Hamann, Sigrid ^{[9
]}

Wenners, Antonia ^{[9
]}

Alkatout, Ibrahim ^{[9
]}

Klapper, Wolfram ^{[10
]}

Rocken, Christoph ^{[10
]}

Bauer, Maret ^{[9
]}

Arnold, Norbert ^{[9
]}

Quintanilla, Miguel ^{[11
]}

Megias, Diego ^{[8
]}

Vicente-Manzanares, Miguel ^{[6
,7
]}

Uriguen, Leyre

Gutkind, J. Silvio ^{[3
,12
]}

Guzman, Manuel ^{[1
,13
,14
]}

Perez-Gomez, Eduardo ^{[1
,2
]}

Sanchez, Cristina ^{[1
,2
]}

机构：

[1] Univ Complutense, Sch Biol, Dept Biochem & Mol Biol 1, Madrid, Spain

[2] Hosp 12 Octubre, Inst Invest, Madrid, Spain

[3] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA

[4] Univ Basque Country UPV EHU, Dept Pharmacol, Bilbao, Spain

[5] Ctr Invest Biomed Red Salud Mental CIBERSAM, Madrid, Spain

[6] Univ Princesa, Sanitaria Hosp, Inst Invest, Madrid, Spain

[7] Univ Autonoma Madrid, Sch Med, Madrid, Spain

[8] Spanish Natl Canc Res Ctr CNIO, Madrid, Spain

[9] Univ Hosp Schleswig Holstein, Dept Gynecol & Obstet, Kiel, Germany

[10] Univ Hosp Schleswig Holstein, Inst Pathol, Kiel, Germany

[11] Univ Autonoma Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid, Spain

[12] Univ Calif San Diego, Dept Pharmacol, Moores Canc Ctr, La Jolla, CA 92093 USA

[13] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Madrid, Spain

[14] IRYCIS, Madrid, Spain

来源：

ONCOTARGET | 2016年 / 7卷 / 30期

关键词：

GPR55; G protein-coupled receptor; cannabinoids; metastasis; triple-negative breast cancer; PROTEIN-COUPLED RECEPTORS; L-ALPHA-LYSOPHOSPHATIDYLINOSITOL; CANNABINOID RECEPTOR; CELL PROLIFERATION; CONCISE GUIDE; PHARMACOLOGY; MIGRATION; LYSOPHOSPHOLIPIDS; ANANDAMIDE; REVEALS;

D O I：

10.18632/oncotarget.10206

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：47565 / 47575

页数：11

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