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 TNERSF10B 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. (C) 2013 Elsevier Inc. All rights reserved.
基金：
National Natural Science Foundation of China (grant number: 81241084), and
from Beijing Natural Science Foundation (grant numbers:
7121005 and 5122016).
第一作者机构：[1]Capital Med Univ, Dept Otolaryngol Head & Neck Surg, Beijing Tongren Hosp, Key Lab Otolaryngol Head & Neck Surg, Beijing, Peoples R China
通讯作者：
通讯机构：[2]Peking Univ, Key Lab Med Immunol, Sch Basic Med Sci,Minist Hlth, Dept Immunol,Hlth Sci Ctr,Ctr Human Dis Genom, Beijing 100871, Peoples R China[3]Chinese Natl Human Genome Ctr CHGB Beijing, Funct Genom Grp, Beijing, Peoples R China
推荐引用方式(GB/T 7714)：
Xu Hongbo,Chen Xiaohong,Huang Junwei,et al.Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2013,436(1):96-103.doi:10.1016/j.bbrc.2013.05.065.
APA：
Xu, Hongbo,Chen, Xiaohong,Huang, Junwei,Deng, Weiwei,Zhong, Qi...&Huang, Zhigang.(2013).Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,436,(1)
MLA：
Xu, Hongbo,et al."Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 436..1(2013):96-103
