title: Identification of GPR65, a novel regulator of matrix metalloproteinases using high through-put screening.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology Head and Neck Surgery, Beijing, China.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Xu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Chen
authors.forename: Junwei
authors.initials: J
authors.lastname: Huang
authors.forename: Weiwei
authors.initials: W
authors.lastname: Deng
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhong
authors.forename: Changli
authors.initials: C
authors.lastname: Yue
authors.forename: Pingzhang
authors.initials: P
authors.lastname: Wang
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: C513334:GPR65 protein, human; D043562:Receptors, G-Protein-Coupled; D018808:Transcription Factor AP-1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3