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Erschienen in: Tumor Biology 9/2016

09.04.2016 | Original Article

Protein phosphatase 4 catalytic subunit is overexpressed in glioma and promotes glioma cell proliferation and invasion

verfasst von: Mengyou Li, Xin Li, Shiming Xu, Pengfei Xue, QingZhe Li, Qingyang Lu, Qingbin Jia, Lianqun Zhang, Xueyuan Li, Xingang Li

Erschienen in: Tumor Biology | Ausgabe 9/2016

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Abstract

Protein phosphatase 4 catalytic subunit (PP4C) has been identified to be overexpressed in various solid cancers. However, to date, the role of PP4C in glioma remains elusive. In the present study, we aimed to detect PP4C expression in glioma patients and explore its function in glioma and prognostic significance in patients with glioma. The expression levels of PP4C mRNA and protein in 30 glioma tissue specimens and 10 non-cancerous brain tissue specimens were detected by qRT-PCR and Western blot analysis. Moreover, immunohistochemistry was performed to assess PP4C expression in 120 glioma patients. The effects of siRNA-mediated PP4C silencing on the proliferation, migration, and invasion of U251 and U87 glioma cells were assessed. We found that PP4C was upregulated in glioma tissue at both mRNA and protein levels compared with non-cancerous brain tissue. Univariate and multivariate analyses indicated that high PP4C expression was an independent prognostic factor for poor survival of glioma patients. Knockdown of PP4C reduced the proliferation, migration, and invasion of U251 and U87 cells. In conclusion, our findings suggest that PP4C plays an oncogenic role in glioma development and progression and might serve as a prognostic biomarker as well as a potential therapeutic target for glioma.
Literatur
1.
Zurück zum Zitat Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.CrossRefPubMedPubMedCentral Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, et al. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007;114:97–109.CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat Moorhead GB, Trinkle-Mulcahy L, Ulke-Lemee A. Emerging roles of nuclear protein phosphatases. Nat Rev Mol Cell Biol. 2007;8:234–44.CrossRefPubMed Moorhead GB, Trinkle-Mulcahy L, Ulke-Lemee A. Emerging roles of nuclear protein phosphatases. Nat Rev Mol Cell Biol. 2007;8:234–44.CrossRefPubMed
3.
Zurück zum Zitat Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR. Centromeric binding and activity of protein phosphatase 4. Nat Commun. 2015;6:5894.CrossRefPubMedPubMedCentral Lipinszki Z, Lefevre S, Savoian MS, Singleton MR, Glover DM, Przewloka MR. Centromeric binding and activity of protein phosphatase 4. Nat Commun. 2015;6:5894.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Toyo-oka K, Mori D, Yano Y, Shiota M, Iwao H, Goto H, et al. Protein phosphatase 4 catalytic subunit regulates cdk1 activity and microtubule organization via ndel1 dephosphorylation. J Cell Biol. 2008;180:1133–47.CrossRefPubMedPubMedCentral Toyo-oka K, Mori D, Yano Y, Shiota M, Iwao H, Goto H, et al. Protein phosphatase 4 catalytic subunit regulates cdk1 activity and microtubule organization via ndel1 dephosphorylation. J Cell Biol. 2008;180:1133–47.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Xie Y, Juschke C, Esk C, Hirotsune S, Knoblich JA. The phosphatase pp4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron. 2013;79:254–65.CrossRefPubMedPubMedCentral Xie Y, Juschke C, Esk C, Hirotsune S, Knoblich JA. The phosphatase pp4c controls spindle orientation to maintain proliferative symmetric divisions in the developing neocortex. Neuron. 2013;79:254–65.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Liao FH, Shui JW, Hsing EW, Hsiao WY, Lin YC, Chan YC, et al. Protein phosphatase 4 is an essential positive regulator for treg development, function, and protective gut immunity. Cell Biosci. 2014;4:25.CrossRefPubMedPubMedCentral Liao FH, Shui JW, Hsing EW, Hsiao WY, Lin YC, Chan YC, et al. Protein phosphatase 4 is an essential positive regulator for treg development, function, and protective gut immunity. Cell Biosci. 2014;4:25.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Theobald B, Bonness K, Musiyenko A, Andrews JF, Urban G, Huang X, et al. Suppression of ser/thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death. Molecular cancer research : MCR. 2013;11:845–55.CrossRefPubMedPubMedCentral Theobald B, Bonness K, Musiyenko A, Andrews JF, Urban G, Huang X, et al. Suppression of ser/thr phosphatase 4 (PP4C/PPP4C) mimics a novel post-mitotic action of fostriecin, producing mitotic slippage followed by tetraploid cell death. Molecular cancer research : MCR. 2013;11:845–55.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Lee DH, Acharya SS, Kwon M, Drane P, Guan Y, Adelmant G, et al. Dephosphorylation enables the recruitment of 53bp1 to double-strand DNA breaks. Mol Cell. 2014;54:512–25.CrossRefPubMedPubMedCentral Lee DH, Acharya SS, Kwon M, Drane P, Guan Y, Adelmant G, et al. Dephosphorylation enables the recruitment of 53bp1 to double-strand DNA breaks. Mol Cell. 2014;54:512–25.CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Yeh PY, Yeh KH, Chuang SE, Song YC, Cheng AL. Suppression of mek/erk signaling pathway enhances cisplatin-induced nf-kappab activation by protein phosphatase 4-mediated nf-kappab p65 thr dephosphorylation. J Biol Chem. 2004;279:26143–8.CrossRefPubMed Yeh PY, Yeh KH, Chuang SE, Song YC, Cheng AL. Suppression of mek/erk signaling pathway enhances cisplatin-induced nf-kappab activation by protein phosphatase 4-mediated nf-kappab p65 thr dephosphorylation. J Biol Chem. 2004;279:26143–8.CrossRefPubMed
10.
Zurück zum Zitat Zhou G, Boomer JS, Tan TH. Protein phosphatase 4 is a positive regulator of hematopoietic progenitor kinase 1. J Biol Chem. 2004;279:49551–61.CrossRefPubMed Zhou G, Boomer JS, Tan TH. Protein phosphatase 4 is a positive regulator of hematopoietic progenitor kinase 1. J Biol Chem. 2004;279:49551–61.CrossRefPubMed
11.
Zurück zum Zitat Bertram PG, Choi JH, Carvalho J, Ai W, Zeng C, Chan TF, et al. Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. J Biol Chem. 2000;275:35727–33.CrossRefPubMed Bertram PG, Choi JH, Carvalho J, Ai W, Zeng C, Chan TF, et al. Tripartite regulation of Gln3p by TOR, Ure2p, and phosphatases. J Biol Chem. 2000;275:35727–33.CrossRefPubMed
12.
Zurück zum Zitat Wang B, Zhao A, Sun L, Zhong X, Zhong J, Wang H, et al. Protein phosphatase PP4 is overexpressed in human breast and lung tumors. Cell Res. 2008;18:974–7.CrossRefPubMed Wang B, Zhao A, Sun L, Zhong X, Zhong J, Wang H, et al. Protein phosphatase PP4 is overexpressed in human breast and lung tumors. Cell Res. 2008;18:974–7.CrossRefPubMed
13.
Zurück zum Zitat Weng S, Wang H, Chen W, Katz MH, Chatterjee D, Lee JE, et al. Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2012;21:1336–43.CrossRefPubMedPubMedCentral Weng S, Wang H, Chen W, Katz MH, Chatterjee D, Lee JE, et al. Overexpression of protein phosphatase 4 correlates with poor prognosis in patients with stage II pancreatic ductal adenocarcinoma. Cancer Epidemiol Biomarkers Prev. 2012;21:1336–43.CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Li X, Liang L, Huang L, Ma X, Li D, Cai S. High expression of protein phosphatase 4 is associated with the aggressive malignant behavior of colorectal carcinoma. Mol Cancer. 2015;14:95.CrossRefPubMedPubMedCentral Li X, Liang L, Huang L, Ma X, Li D, Cai S. High expression of protein phosphatase 4 is associated with the aggressive malignant behavior of colorectal carcinoma. Mol Cancer. 2015;14:95.CrossRefPubMedPubMedCentral
15.
16.
Zurück zum Zitat Hu MC, Tang-Oxley Q, Qiu WR, Wang YP, Mihindukulasuriya KA, Afshar R, et al. Protein phosphatase x interacts with c-Rel and stimulates c-Rel/nuclear factor kappab activity. J Biol Chem. 1998;273:33561–5.CrossRefPubMed Hu MC, Tang-Oxley Q, Qiu WR, Wang YP, Mihindukulasuriya KA, Afshar R, et al. Protein phosphatase x interacts with c-Rel and stimulates c-Rel/nuclear factor kappab activity. J Biol Chem. 1998;273:33561–5.CrossRefPubMed
17.
Zurück zum Zitat Knight LM, Stakaityte G, Wood JJ, Abdul-Sada H, Griffiths DA, Howell GJ, et al. Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration. J Virol. 2015;89:35–47.CrossRefPubMed Knight LM, Stakaityte G, Wood JJ, Abdul-Sada H, Griffiths DA, Howell GJ, et al. Merkel cell polyomavirus small T antigen mediates microtubule destabilization to promote cell motility and migration. J Virol. 2015;89:35–47.CrossRefPubMed
18.
Zurück zum Zitat Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D. A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol. 2010;17:365–72.CrossRefPubMedPubMedCentral Lee DH, Pan Y, Kanner S, Sung P, Borowiec JA, Chowdhury D. A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat Struct Mol Biol. 2010;17:365–72.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Shaltiel IA, Aprelia M, Saurin AT, Chowdhury D, Kops GJ, Voest EE, et al. Distinct phosphatases antagonize the p53 response in different phases of the cell cycle. Proc Natl Acad Sci U S A. 2014;111:7313–8.CrossRefPubMedPubMedCentral Shaltiel IA, Aprelia M, Saurin AT, Chowdhury D, Kops GJ, Voest EE, et al. Distinct phosphatases antagonize the p53 response in different phases of the cell cycle. Proc Natl Acad Sci U S A. 2014;111:7313–8.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, et al. A PP4-phosphatase complex dephosphorylates gamma-h2ax generated during DNA replication. Mol Cell. 2008;31:33–46.CrossRefPubMedPubMedCentral Chowdhury D, Xu X, Zhong X, Ahmed F, Zhong J, Liao J, et al. A PP4-phosphatase complex dephosphorylates gamma-h2ax generated during DNA replication. Mol Cell. 2008;31:33–46.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Rosales KR, Reid MA, Yang Y, Tran TQ, Wang WI, Lowman X, et al. Tiprl inhibits protein phosphatase 4 activity and promotes h2ax phosphorylation in the DNA damage response. PLoS ONE. 2015;10, e0145938.CrossRefPubMedPubMedCentral Rosales KR, Reid MA, Yang Y, Tran TQ, Wang WI, Lowman X, et al. Tiprl inhibits protein phosphatase 4 activity and promotes h2ax phosphorylation in the DNA damage response. PLoS ONE. 2015;10, e0145938.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Lee J, Adelmant G, Marto JA, Lee DH. Dephosphorylation of DBC1 by protein phosphatase 4 is important for p53-mediated cellular functions. Mol Cells. 2015;38:697–704.CrossRefPubMedPubMedCentral Lee J, Adelmant G, Marto JA, Lee DH. Dephosphorylation of DBC1 by protein phosphatase 4 is important for p53-mediated cellular functions. Mol Cells. 2015;38:697–704.CrossRefPubMedPubMedCentral
Metadaten
Titel
Protein phosphatase 4 catalytic subunit is overexpressed in glioma and promotes glioma cell proliferation and invasion
verfasst von
Mengyou Li
Xin Li
Shiming Xu
Pengfei Xue
QingZhe Li
Qingyang Lu
Qingbin Jia
Lianqun Zhang
Xueyuan Li
Xingang Li
Publikationsdatum
09.04.2016
Verlag
Springer Netherlands
Erschienen in
Tumor Biology / Ausgabe 9/2016
Print ISSN: 1010-4283
Elektronische ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-016-5054-6

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