TPX2 regulates tumor growth in human cervical carcinoma cells

Jiang,Peiyue; Shen,Kexin; Wang,Xuerui; Song,Haiqin; Yue,Ying; Liu,Tongjun

doi:10.3892/mmr.2014.2106

TPX2 regulates tumor growth in human cervical carcinoma cells

Authors:
- Peiyue Jiang
- Kexin Shen
- Xuerui Wang
- Haiqin Song
- Ying Yue
- Tongjun Liu
View Affiliations

Affiliations: Department of Gynecological Oncology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China, Department of Ophthalmology, China-Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China
Published online on: April 2, 2014 https://doi.org/10.3892/mmr.2014.2106
Pages: 2347-2351

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The targeting protein for the Xenopus kinesin‑like protein 2 (TPX2), a microtubule-associated protein, has been utilized as a tool to evaluate, more precisely, the proliferative behavior of tumor cells. The abnormal expression of TPX2 in a variety of malignant tumor types has been reported, however less is known about its role in cervical cancer. In the present study, the association between TPX2 expression and the biological behavior of cervical cancer, was investigated. Immunohistochemistry and RT-PCR were used to detect the expression of TPX2 in cervical cancer tissues. The inhibitory effect of TPX2-siRNA on the growth of SiHa human cervical carcinoma cells was studied in vitro. TPX2 expression was identified as significantly higher in cervical carcinoma compared with the control, normal cervical tissues. TPX2 siRNA transfected into SiHa cells induced apoptosis and inhibited cell proliferation and invasion. Similar results were obtained by in vivo transplantation, as TPX2 siRNA transfection significantly reduced tumor growth of the xenograft in nude mice. The results demonstrated that TPX2 is important in the regulation of tumor growth in cervical cancer and therefore may be a potential therapeutic target as a novel treatment strategy.

View Figures

View References

1	Kufer TA, Silljé HH, Körner R, Gruss OJ, Meraldi P and Nigg EA: Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol. 158:617–623. 2002. View Article : Google Scholar : PubMed/NCBI
2	Ma Y, Lin D, Sun W, et al: Expression of targeting protein for xklp2 associated with both malignant transformation of respiratory epithelium and progression of squamous cell lung cancer. Clin Cancer Res. 12:1121–1127. 2006. View Article : Google Scholar : PubMed/NCBI
3	Mohsenifar J, Almassi-Aghdam M, Mohammad-Taheri Z, et al: Prognostic values of proliferative markers ki-67 and repp86 in breast cancer. Arch Iran Med. 10:27–31. 2007.PubMed/NCBI
4	Shigeishi H, Ohta K, Hiraoka M, et al: Expression of TPX2 in salivary gland carcinomas. Oncol Rep. 21:341–344. 2009.PubMed/NCBI
5	Aguirre-Portolés C, Bird AW, Hyman A, Cañamero M, Pérez de Castro I and Malumbres M: Tpx2 controls spindle integrity, genome stability, and tumor development. Cancer Res. 72:1518–1528. 2012.PubMed/NCBI
6	Zhang L, Huang H, Deng L, et al: TPX2 in malignantly transformed human bronchial epithelial cells by anti-benzo[a]pyrene-7,8-diol-9,10-epoxide. Toxicology. 252:49–55. 2008.PubMed/NCBI
7	Li L, Yang G, Ren C, et al: Glioma pathogenesis-related protein 1 induces prostate cancer cell death through Hsc70-mediated suppression of AURKA and TPX2. Mol Oncol. 7:484–496. 2013. View Article : Google Scholar : PubMed/NCBI
8	Chang H, Wang J, Tian Y, Xu J, Gou X and Cheng J: The TPX2 gene is a promising diagnostic and therapeutic target for cervical cancer. Oncol Rep. 27:353–1359. 2012.PubMed/NCBI
9	Gruss OJ and Vernos I: The mechanism of spindle assembly: functions of Ran and its target TPX2. J Cell Biol. 166:949–955. 2004. View Article : Google Scholar : PubMed/NCBI
10	Gruss OJ, Carazo-Salas RE, Schatz CA, et al: Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. Cell. 104:83–93. 2001. View Article : Google Scholar : PubMed/NCBI
11	Bayliss R, Sardon T, Ebert J, Lindner D, Vernos I and Conti E: Determinants for Aurora-A activation and Aurora-B discrimination by TPX2. Cell Cycl. 3:404–407. 2004.PubMed/NCBI
12	Tonon G, Wong KK, Maulik G, et al: High-resolution genomic profiles of human lung cancer. Proc Natl Acad Sci USA. 102:9625–9630. 2005. View Article : Google Scholar : PubMed/NCBI
13	Scharer CD, Laycock N, Osunkoya AO, et al: Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells. J Transl Med. 6:792008. View Article : Google Scholar : PubMed/NCBI
14	Warner SL, Stephens BJ, Nwokenkwo S, et al: Validation of TPX2 as a potential therapeutic target in pancreatic cancer cells. Clin Cancer Res. 15:6519–6528. 2009. View Article : Google Scholar : PubMed/NCBI
15	Stuart JE, Lusis EA, Scheck AC, et al: Identification of gene markers associated with aggressive meningioma by filtering across multiple sets of gene expression arrays. J Neuropathol Exp Neurol. 70:1–12. 2011. View Article : Google Scholar : PubMed/NCBI
16	Li B, Qi XQ, Chen X, et al: Expression of targeting protein for Xenopus kinesin-like protein 2 is associated with progression of human malignant astrocytoma. Brain Res. 1352:200–207. 2010. View Article : Google Scholar : PubMed/NCBI
17	Brizova H, Kalinova M, Krskova L, Mrhalova M and Kodet R: A novel quantitative PCR of proliferation markers (Ki-67, topoisomerase IIalpha, and TPX2): an immunohistochemical correlation, testing, and optimizing for mantle cell lymphoma. Virchows Arch. 456:671–679. 2010. View Article : Google Scholar : PubMed/NCBI
18	Satow R, Shitashige M, Kanai Y, et al: Combined functional genome survey of therapeutic targets for hepatocellular carcinoma. Clin Cancer Res. 16:2518–2528. 2010. View Article : Google Scholar : PubMed/NCBI
19	Shigeishi H, Fujimoto S, Hiraoka M, et al: Overexpression of the receptor for hyaluronan-mediated motility, correlates with expression of microtubule-associated protein in human oral squamous cell carcinomas. Int J Oncol. 34:1565–1571. 2009. View Article : Google Scholar : PubMed/NCBI
20	Smith LT, Mayerson J, Nowak NJ, et al: 20q11.1 amplification in giant-cell tumor of bone: Array CGH, FISH, and association with outcome. Genes Chromosomes Cancer. 45:957–966. 2006. View Article : Google Scholar : PubMed/NCBI
21	Wei P, Zhang N, Xu Y, et al: TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer. J Transl Med. 11:3132013. View Article : Google Scholar : PubMed/NCBI
22	Morgan-Lappe SE, Tucker LA, Huang X, et al: Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res. 67:4390–4398. 2007. View Article : Google Scholar : PubMed/NCBI