title: Protein kinase D2 promotes the proliferation of glioma cells by regulating Golgi phosphoprotein 3.
abstract: Protein kinase D2 (PKD2) has been demonstrated to promote tumorigenesis in many types of cancers. However, how PKD2 regulates cancer cell growth is largely unknown. In this study, we found that over-expression of PKD2 promoted glioma cell growth but down-regulation of PKD2 inhibited it. Further investigation indicated that PKD2 down-regulation decreased the protein level of Golgi phosphoprotein 3(GOLPH3) as well as p-AKT level. On the contrary, over-expression of PKD2 increased the protein level of GOLPH3 and p-AKT. In addition, GOLPH3 exhibited similar effect on glioma cell growth to that of PKD2. Importantly, GOLPH3 down-regulation partially abolished glioma cell proliferation induced by PKD2 over-expression, while over-expression of GOLPH3 also partially rescued the inhibition effect of PKD2 down-regulation on glioma cell growth. Interestingly, the level of PKD2 and GOLPH3 significantly increased and was positively correlated in a cohort of glioma patients, as well as in patients from TCGA database. Taken together, these results reveal that PKD2 promotes glioma cell proliferation by regulating GOLPH3 and then AKT activation. Our findings indicate that both PKD2 and GOLPH3 play important roles in the progression of human gliomas and PKD2-GOLPH3-AKT signaling pathway might be a potential glioma therapeutic target.
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: xpzhou@xzmc.edu.cn.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Xue
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Minglin
authors.initials: M
authors.lastname: Yang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Lu
authors.affiliation: The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Zhaohao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Jinxia
authors.initials: J
authors.lastname: Hu
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Shao
authors.initials: S
authors.lastname: Xie
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China.
authors.forename: Wenjian
authors.initials: W
authors.lastname: Zhan
authors.affiliation: Brain Hospital, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu, China; Insititute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China. Electronic address: yu.rutong@163.com.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D000091283:Protein Kinase D2; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D014162:Transfection
chemical_list: C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D000091283:Protein Kinase D2; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: AKT; GOLPH3; Glioblastoma; PKD2; Proliferation