Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.
Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer.
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DOI：
10.18632/oncotarget.10206
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发表时间：
2016-07-26
期刊：
影响因子：
--
通讯作者：
Sánchez C
中科院分区：
文献类型：
--
作者：
Andradas C;Blasco-Benito S;Castillo-Lluva S;Dillenburg-Pilla P;Diez-Alarcia R;Juanes-García A;García-Taboada E;Hernando-Llorente R;Soriano J;Hamann S;Wenners A;Alkatout I;Klapper W;Rocken C;Bauer M;Arnold N;Quintanilla M;Megías D;Vicente-Manzanares M;Urigüen L;Gutkind JS;Guzmán M;Pérez-Gómez E;Sánchez C
孤儿G蛋白偶联受体GPR55与驱动恶性生长的基本改变直接或间接相关：不受控制的癌细胞增殖、持续的血管生成以及癌细胞粘附和迁移。然而，人们对这种受体在转移中的参与知之甚少。在这里，我们发现人类肿瘤中 GPR55 表达升高与侵袭性基底/三阴性乳腺癌群体、发生转移的可能性较高以及患者预后不良相关。 GPR55 被其提议的内源性配体溶血磷脂酰肌醇激活，在体外和体内赋予乳腺癌细胞促侵袭特征。具体来说，这种效应是通过与 Gq/11 异三聚体蛋白偶联并随后通过 ERK 激活转录因子 ETV4/PEA3 来引发的。总之，这些数据表明 GPR55 促进乳腺癌转移，并支持这种孤儿受体可能构成高度侵袭性三阴性亚型的新治疗靶点和潜在生物标志物的观点。
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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影响因子：
7.3
作者：
Kargl J;Andersen L;Hasenöhrl C;Feuersinger D;Stančić A;Fauland A;Magnes C;El-Heliebi A;Lax S;Uranitsch S;Haybaeck J;Heinemann A;Schicho R
通讯作者：
Schicho R
DOI：
10.1124/jpet.110.172650
发表时间：
2011-04-01
影响因子：
3.5
作者：
Brown, Andrew J.;Daniels, Dion A.;Dowell, Simon J.
通讯作者：
Dowell, Simon J.
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
4.8
作者：
Henstridge, Christopher M.;Balenga, Nariman A. B.;Irving, Andrew J.
通讯作者：
Irving, Andrew J.
影响因子：
7.5
作者：
O'Hayre, Morgan;Degese, Maria S.;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio