title: Golgi phosphoprotein 3 regulates metastasis of prostate cancer via matrix metalloproteinase 9.
abstract: Recent studies suggest that Golgi phosphoprotein 3 (GOLPH3) protein is a candidate metastasis gene in human cancer. The goal of this study was to determine the function of GOLPH3 in prostate cancer metastasis and to identify GOLPH3-regulated pathways and genes involved in prostate cancer metastasis. GOLPH3 expression was detected in prostate cancer. To investigate its function, PC-3 cells were stably transfected with shRNA targeting GOLPH3. Cell abilities of invasion and migration were measured in vitro. Downstream regulatory pathways of GOLPH3 were characterized using quantitative RT-PCR and Western blotting analysis. Immunohistochemical studies in prostate cancer specimens revealed a positive correlation of GOLPH3 expression with prostate cancer. GOLPH3 was expressed in prostate cancer cell lines. GOLPH3 repression resulted in the reduction of mRNA level and protein level of MMP9, accompanied with reduced phosphorylation of mTOR, EGFR and Src. Our findings suggest GOLPH3 regulate MMP9 expression which impact cell migration and invasion. This regulation is probably mediated by EGFR and Src signaling pathways.
authors.affiliation: Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200011, China ; Department of Urology, Linyi People's Hospital Linyi 276000, China.
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Urology, Linyi People's Hospital Linyi 276000, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qi
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University Shanghai 201508, China.
authors.forename: Zhanyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200011, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gu
authors.affiliation: Department of Urology, Jinshan Hospital, Fudan University Shanghai 201508, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Urology, Linyi People's Hospital Linyi 276000, China.
authors.forename: Fengfu
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Urology, Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University Shanghai 200011, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wang
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D066246:ErbB Receptors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D058570:TOR Serine-Threonine Kinases; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; C546842:MTOR protein, human; D066246:ErbB Receptors; D019061:src-Family Kinases; D058570:TOR Serine-Threonine Kinases; D020780:Matrix Metalloproteinase 9
keywords: EGFR; GOLPH3; MMP9; mTOR; metastasis; prostate cancer