β‑transducin repeat‑containing E3 ubiquitin protein ligase inhibits migration, invasion and proliferation of glioma cells

Liang,Jun; Wang,Wei‑Feng; Xie,Shao; Zhang,Xian‑Li; Qi,Wei‑Feng; Zhou,Xiu‑Ping; Hu,Jin‑Xia; Shi,Qiong; Yu,Ru‑Tong

doi:10.3892/ol.2017.6533

β‑transducin repeat‑containing E3 ubiquitin protein ligase inhibits migration, invasion and proliferation of glioma cells

Authors:
- Jun Liang
- Wei‑Feng Wang
- Shao Xie
- Xian‑Li Zhang
- Wei‑Feng Qi
- Xiu‑Ping Zhou
- Jin‑Xia Hu
- Qiong Shi
- Ru‑Tong Yu
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Affiliations: Department of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Laboratory of Neurosurgery, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China
Published online on: July 7, 2017 https://doi.org/10.3892/ol.2017.6533
Pages: 3131-3135

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Abstract

β‑transducin repeat‑containing E3 ubiquitin protein ligase (β‑TrCP) serves as the substrate recognition subunit for the Skp1‑Cullin1‑F‑box protein E3 ubiquitin ligase, which recognizes the double phosphorylated DSG (X)2+nS destruction motif in various substrates that are essential for numerous aspects of tumorigenesis and regulates several important signaling pathways. However, the biological significance of β‑TrCP in glioma progression remains largely unknown. A previous study by the authors demonstrated that the levels of β‑TrCP protein expression in brain glioma tissues were significantly lower compared with non‑tumorous tissues and that higher grades of gliomas exhibited lower levels of β‑TrCP expression in comparison with lower glioma grades. In addition, low β‑TrCP expression was associated with poor prognosis in patients with glioma. Subsequently, the present study aimed to investigate the effect of β‑TrCP on migratory, invasive and proliferative abilities of glioma cells. β‑TrCP plasmids were transfected into cultured U251 and U87 glioma cells, and changes in migration, invasion and proliferation were analyzed using wound healing, Transwell and EdU assays. It was identified that the overexpression of β‑TrCP inhibited migration, invasion and proliferation in glioma cells. In summary, these results indicate that β‑TrCP may serve a protective role against the progression of glioma by suppressing cell migration, invasion and proliferation. The potential mechanism of β‑TrCP I glioma cells requires additional investigation.

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1	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2008. View Article : Google Scholar : PubMed/NCBI
2	Buonerba C, Di Lorenzo G, Marinelli A, Federico P, Palmieri G, Imbimbo M, Conti P, Peluso G, De Placido S and Sampson JH: A comprehensive outlook on intracerebral therapy of malignant gliomas. Crit Rev OncolHematol. 80:54–68. 2011. View Article : Google Scholar
3	Sherman JH, Hoes K, Marcus J, Komotar RJ, Brennan CW and Gutin PH: Neurosurgery for brain tumors: Update on recent technical advances. Curr Neurol Neurosci Rep. 11:313–319. 2011. View Article : Google Scholar : PubMed/NCBI
4	Onishi M, Ichikawa T, Kurozumi K and Date I: Angiogenesis and invasion in glioma. Brain Tumor Pathol. 28:13–24. 2011. View Article : Google Scholar : PubMed/NCBI
5	Kim CS, Jung S, Jung TY, Jang WY, Sun HS and Ryu HH: Characterization of invading glioma cells using molecular analysis of leading-edge tissue. J Korean Neurosurg Soc. 50:157–165. 2011. View Article : Google Scholar : PubMed/NCBI
6	Ohgaki H and Kleihues P: Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 64:479–489. 2005. View Article : Google Scholar : PubMed/NCBI
7	Rutka JT, Taylor M, Mainprize T, Langlois A, Ivanchuk S, Mondal S and Dirks P: Molecular biology and neurosurgery in the third millennium. Neurosurgery. 46:1034–1051. 2000. View Article : Google Scholar : PubMed/NCBI
8	Liu C, Kato Y, Zhang Z, Do VM, Yankner BA and He X: beta-Trcp couples beta-catenin phosphorylation-degradation and regulates Xenopus axis formation. Proc Natl Acad Sci USA. 96:6273–6278. 1999. View Article : Google Scholar : PubMed/NCBI
9	Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M and Draetta GF: Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature. 426:87–91. 2003. View Article : Google Scholar : PubMed/NCBI
10	Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T and Osada H: M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCF beta-TrCP. Proc Natl Acad Sci USA. 101:4419–4424. 2004. View Article : Google Scholar : PubMed/NCBI
11	Chiaur DS, Murthy S, Cenciarelli C, Parks W, Loda M, Inghirami G, Demetrick D and Pagano M: Five human genes encoding F-box proteins: Chromosome mapping and analysis in human tumors. Cytogenet Cell Genet. 88:255–258. 2000. View Article : Google Scholar : PubMed/NCBI
12	Koike J, Sagara N, Kirikoshi H, Takagi A, Miwa T, Hirai M and Katoh M: Molecular cloning and genomic structure of the betaTRCP2 gene on chromosome 5q35.1. Biochem Biophys Res Commun. 269:103–109. 2000. View Article : Google Scholar : PubMed/NCBI
13	Ballarino M, Marchioni M and Carnevali F: The Xenopus laevis beta TrCP gene: Genomic organization, alternative splicing, 5′ and 3′ region characterization and comparison of its structure with that of human beta TrCP genes. Biochim Biophys Acta. 1577:81–92. 2002. View Article : Google Scholar : PubMed/NCBI
14	Deshaies RJ: SCF and Cullin/Ring H2-based ubiquitin ligases. Annu Rev Cell Dev Biol. 15:435–467. 1999. View Article : Google Scholar : PubMed/NCBI
15	Fuchs SY, Spiegelman VS and Kumar KG: The many faces of beta-TrCP E3 ubiquitin ligases: Reflections in the magic mirror of cancer. Oncogene. 23:2028–2036. 2004. View Article : Google Scholar : PubMed/NCBI
16	Cenciarelli C, Chiaur DS, Guardavaccaro D, Parks W, Vidal M and Pagano M: Identification of a family of human F-box proteins. Curr Biol. 9:1177–1179. 1999. View Article : Google Scholar : PubMed/NCBI
17	DeSalle LM and Pagano M: Regulation of the G1 to S transition by the ubiquitin pathway. FEBS Lett. 490:179–189. 2001. View Article : Google Scholar : PubMed/NCBI
18	Pickart CM: Mechanisms underlying ubiquitination. Annu Rev Biochem. 70:503–533. 2001. View Article : Google Scholar : PubMed/NCBI
19	Ciechanover A, Orian A and Schwartz AL: Ubiquitin-mediated proteolysis: Biological regulation via destruction. Bioessays. 22:442–451. 2000. View Article : Google Scholar : PubMed/NCBI
20	Zhou P: Targeted protein degradation. Curr Opin Chem Biol. 9:51–55. 2005. View Article : Google Scholar : PubMed/NCBI
21	Hershko A and Ciechanover A: The ubiquitin system. Annu Rev Biochem. 67:425–479. 1998. View Article : Google Scholar : PubMed/NCBI
22	Maniatis T: A ubiquitin ligase complex essential for the NF-kappaB, Wnt/Wingless and Hedgehog signaling pathways. Genes Dev. 13:505–510. 1999. View Article : Google Scholar : PubMed/NCBI
23	Sahasrabuddhe AA, Dimri M, Bommi PV and Dimri GP: βTrCP regulates BMI1 protein turnover via ubiquitination and degradation. Cell Cycle. 10:1322–1330. 2011. View Article : Google Scholar : PubMed/NCBI
24	Fuchs SY, Chen A, Xiong Y, Pan ZQ and Ronai Z: HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene. 18:2039–2046. 1999. View Article : Google Scholar : PubMed/NCBI
25	Hart M, Concordet JP, Lassot I, Albert I, del los Santos R, Durand H, Perret C, Rubinfeld B, Margottin F, Benarous R and Polakis P: The F-box protein beta-TrCP associates with phosphorylated beta-catenin and regulates its activity in the cell. Curr Biol. 9:207–210. 1999. View Article : Google Scholar : PubMed/NCBI
26	Latres E, Chiaur DS and Pagano M: The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene. 18:849–854. 1999. View Article : Google Scholar : PubMed/NCBI
27	Shaik S, Nucera C, Inuzuka H, Gao D, Garnaas M, Frechette G, Harris L, Wan L, Fukushima H, Husain A, et al: SCF (β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2. J Exp Med. 209:1289–1307. 2012. View Article : Google Scholar : PubMed/NCBI
28	Zhong J, Shaik S, Wan L, Tron AE, Wang Z, Sun L, Inuzuka H and Wei W: SCF β-TRCP targets MTSS1 for ubiquitination-mediated destruction to regulate cancer cell proliferation and migration. Oncotarget. 4:2339–2353. 2013. View Article : Google Scholar : PubMed/NCBI
29	Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD and Jackson PK: Prophase destruction of Emi1 by the SCF (betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell. 4:813–826. 2003. View Article : Google Scholar : PubMed/NCBI
30	Xu Y, Lee SH, Kim HS, Kim NH, Piao S, Park SH, Jung YS, Yook JI, Park BJ and Ha NC: Role of CK1 in GSK3beta-mediated phosphorylation and degradation of snail. Oncogene. 29:3124–3133. 2010. View Article : Google Scholar : PubMed/NCBI
31	He N, Li C, Zhang X, Sheng T, Chi S, Chen K, Wang Q, Vertrees R, Logrono R and Xie J: Regulation of lung cancer cell growth and invasiveness by beta-TRCP. Mol Carcinog. 42:18–28. 2005. View Article : Google Scholar : PubMed/NCBI
32	Liang J, Wang WF, Xie S, Zhang XL, Qi WF, Zhou XP, Hu JX, Shi Q and Yu RT: Expression of β-transducin repeat-containing E3 ubiquitin protein ligase in human glioma and its correlation with prognosis. Oncol Lett. 9:2651–2656. 2015.PubMed/NCBI
33	Li X, Liu J and Gao T: beta-TrCP-mediated ubiquitination and degradation of PHLPP1 are negatively regulated by Akt. Mol Cell Biol. 29:6192–6205. 2009. View Article : Google Scholar : PubMed/NCBI
34	Gluschnaider U, Hidas G, Cojocaru G, Yutkin V, Ben-Neriah Y and Pikarsky E: beta-TrCP inhibition reduces prostate cancer cell growth via upregulation of the aryl hydrocarbon receptor. PLoS One. 5:e90602010. View Article : Google Scholar : PubMed/NCBI
35	Wan M, Huang J, Jhala NC, Tytler EM, Yang L, Vickers SM, Tang Y, Lu C, Wang N and Cao X: SCF(beta-TrCP1) controls Smad4 protein stability in pancreatic cancer cells. Am J Pathol. 166:1379–1392. 2005. View Article : Google Scholar : PubMed/NCBI
36	Ruiz P and Günthert U: The cellular basis of metastasis. World J Urol. 14:141–150. 1996. View Article : Google Scholar : PubMed/NCBI