Oncogene：GPR55在皮肤肿瘤的发生中具有至关重要的意义

G蛋白偶联受体（GPCRs）控制重要的生理过程，一旦其功能发生障碍后会出现各种疾病包括癌症。孤儿G蛋白偶联受体GPR55十多年前就已经被发现确定，但关于其与生理病理的相关作用却一直了解不多。

最近表明GPR55控制体外培养和异种移植的人癌症细胞株的生物学行为。然而，有关这种受体在体内恶变的实际作用的研究因为缺乏临床相关模型而一再受到阻扰。近日Oncogene杂志上的一则研究证实GPR55驱动小鼠皮肤肿瘤的发展。GPR55基因缺陷小鼠比野生型老鼠更能抵抗DMBA/TPA诱导的乳头状瘤的形成。GPR55的促肿瘤作用主要是由于其对癌细胞的增殖优势。

此外，GPR55能增强皮肤癌细胞的锚定独立生长、侵袭和体内致瘤能力，这表明它不仅促进肿瘤的发展，而且对肿瘤的侵袭也至关重要。最后研究还发现相比于健康组织，GPR55在人皮肤肿瘤和其他人鳞状细胞癌中都存在相应的表达上调。

总之，这些研究结果表明GPR55在皮肤肿瘤的发生发展中具有至关重要的意义，这种受体可以作为一种新的生物标志物来诊断治疗鳞状细胞癌。

doi:10.1038/onc.2012.278
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The orphan receptor GPR55 drives skin carcinogenesis and is upregulated in human squamous cell carcinomas.

Pérez-Gómez E, Andradas C, Flores JM, Quintanilla M, Paramio JM, Guzmán M, Sánchez C.

G protein-coupled receptors (GPCRs) control crucial physiological processes and their dysfunction contributes to various human diseases, including cancer. The orphan GPCR GPR55 was identified and cloned more than a decade ago, but very little is known about its physio-pathological relevance. It has been recently shown that GPR55 controls the behavior of human cancer cell lines in culture and xenografts. However, the assessment of the actual role of this receptor in malignant transformation in vivo is hampered by the lack of studies on its functional impact in clinically-relevant models of cancer. Here we demonstrate that GPR55 drives mouse skin tumor development. Thus, GPR55-deficient mice were more resistant to DMBA/TPA-induced papilloma and carcinoma formation than their wild-type littermates. GPR55 exerted this pro-tumor effect primarily by conferring a proliferative advantage on cancer cells. In addition, GPR55 enhanced skin cancer cell anchorage-independent growth, invasiveness and tumorigenicity in vivo, suggesting that it promotes not only tumor development but also tumor aggressiveness. Finally, we observed that GPR55 is upregulated in human skin tumors and other human squamous cell carcinomas compared with the corresponding healthy tissues. Altogether, these findings reveal the pivotal importance of GPR55 in skin tumor development, and suggest that this receptor may be used as a new biomarker and therapeutic target in squamous cell carcinomas.