Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis
Up-regulation of GPR48 induced by down-regulation of p27Kip1 enhances carcinoma cell invasiveness and metastasis
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DOI：
10.1158/0008-5472.can-06-2629
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发表时间：
2006-12-15
期刊：
影响因子：
11.2
通讯作者：
Kitagawa, Masatoshi
中科院分区：
文献类型：
--
作者：
Gao, Yun;Kitagawa, Kyoko;Kitagawa, Masatoshi
细胞周期蛋白依赖性激酶抑制剂P27（Kip 1）的表达水平降低与各种类型癌症患者的肿瘤恶性程度增加和预后不良相关。为了研究这种关系的基础，我们应用微阵列分析来筛选p27（+/-）和亲本（p27（+/+））HCT 116人结肠癌细胞之间差异表达的基因。在p27（+/-）细胞中G蛋白偶联受体48（GPR 48）基因的表达增加。GPR 48的强制表达增加了HCT 116细胞的体外侵袭活性和肺转移潜能。相反，通过RNA干扰去除内源性GPR 48降低了HeLa和刘易斯肺癌细胞的侵袭潜力，不仅在体外，而且在体内。此外，GPR 48表达与淋巴结转移显著相关，与p27表达呈负相关。因此，GPR 48可能在肿瘤的侵袭和转移中起重要作用，因此可能代表潜在的预后标志物或治疗靶点。
A reduced expression level of the cyclin-dependent kinase inhibitor P27(Kip1) is associated with increased tumor malignancy and poor prognosis in individuals with various types of cancer. To investigate the basis for this relation, we applied microarray analysis to screen for genes differentially expressed between p27(+/-) and parental (p27(+/+)) HCT116 human colon carcinoma cells. Expression of the gene for G protein-coupled receptor 48 (GPR48) was increased in the p27(+/-) cells. Forced expression of GPR48 increased both in vitro invasive activity and lung metastasis potency of HCT116 cells. In contrast, depletion of endogenous GPR48 by RNA interference reduced the invasive potential of HeLa and Lewis lung carcinoma cells not only in vitro but also in vivo. Moreover, GPR48 expression was significantly associated with lymph node metastasis and inversely correlated with p27 expression in human colon carcinomas. GPR48 may thus play an important role in invasiveness and metastasis of carcinoma and might therefore represent a potential prognostic marker or therapeutic target.