Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.
Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.
复制标题
DOI：
10.1016/j.bbrc.2013.05.065
复制
发表时间：
2013-06
影响因子：
3.1
通讯作者：
Hongbo Xu;Xiaohong Chen;Junwei Huang;Weiwei Deng;Q. Zhong;C. Yue;Pingzhang Wang;Zhigang Huang
中科院分区：
文献类型：
--
作者：
Hongbo Xu;Xiaohong Chen;Junwei Huang;Weiwei Deng;Q. Zhong;C. Yue;Pingzhang Wang;Zhigang Huang
基质金属蛋白酶（MMPs）在几乎所有癌症中都过表达。为了研究头颈癌（HNC）中MMP表达的新调控因子，我们在双荧光素酶测定系统中使用MMP启动子报告基因筛选了636个候选基因，这些基因编码了推测的人跨膜蛋白。三个基因GPR65、AXL和TNFRSF10B显著激活了MMP3的表达诱导。在A549和/或FaDu细胞中进一步证实GPR65对MMP表达的诱导作用。酸性条件下GPR65介导MMP诱导。MMP3启动子AP-1结合位点对MMP3诱导至关重要。GPR65重组腺病毒感染A549细胞后，细胞侵袭速度加快。综上所述，我们验证了GPR65是MMP3上游的重要调控基因，并确定了质子传感g蛋白偶联受体调控MMP3的新机制。
Matrix metalloproteinases (MMPs) are over-expressed in nearly all cancers. To study novel regulatory factors of MMP expression in head and neck cancer (HNC), we screened a total of 636 candidate genes encoding putative human transmembrane proteins using MMP promoter reporter in a dual luciferase assay system. Three genes GPR65, AXL and TNFRSF10B dramatically activated the induction of MMP3 expression. The induction of MMP expression by GPR65 was further confirmed in A549 and/or FaDu cells. GPR65 mediated MMP induction under acidic conditions. The AP-1 binding site in MMP3 promoter was crucial for MMP3 induction. Moreover, the A549 cells infected by recombinant adenovirus of GPR65 showed accelerated cell invasion. In conclusion, we validate that GPR65 is vital regulatory genes upstream of MMP3, and define a novel mechanism of MMP3 regulation by proton-sensing G-protein-coupled receptors.