Identification of WISP1 as a novel oncogene in glioblastoma

Jing,Di; Zhang,Qian; Yu,Haiming; Zhao,Yajie; Shen,Liangfang

doi:10.3892/ijo.2017.4119

Identification of WISP1 as a novel oncogene in glioblastoma

Authors:
- Di Jing
- Qian Zhang
- Haiming Yu
- Yajie Zhao
- Liangfang Shen
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Affiliations: Department of Oncology Radiotherapy, Xiangya Hospital of Central South University, Changsha, Hunan 410008, P.R. China, Teaching and Research Section of Surgery, Xiangnan University Affiliated Hospital, Chenzhou, Hunan 423000, P.R. China, Department of Critical Care Medicine, Hunan Provincial Peopel's Hospital, Changsha, Hunan 410005, P.R. China, Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: September 5, 2017 https://doi.org/10.3892/ijo.2017.4119
Pages: 1261-1270

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Abstract

Glioblastoma is the most common and aggressive primary brain tumor and has a high mortality in humans. However, mechanisms and factors involved in the progression of glioblastoma remain elusive. WISP1 (WNT1 inducible signaling pathway protein 1), has been suggested to be a critical regulator of cancer development. The aim of this study was to investigate the role of WISP1 in regulating the progression of glioblastoma. Clinicopathological characteristics of glioblastoma were assessed, and higher levels of WISP1 were positively associated with advanced clinical stage and a poor prognosis. Consistently, WISP1 expression was significantly upregulated in glioblastoma tissue and cell lines compared with normal tissue and cells. Additionally, inhibition of WISP1 greatly suppressed cell proliferation, migration, and invasion and promoted apoptosis and cell cycle arrest of glioblastoma cells. Further study indicated that downregulation of WISP1 suppressed cell proliferation associated with the gene expression of c‑myc and cyclin D1 and cellular signaling such as through the ERK pathway, while inhibiting epithelial-mesenchymal transition and MMP9. Finally, knockdown of WISP1 markedly suppressed in vivo tumor growth and sensitized glioblastoma cells to temozolomide. This study identified WISP1 as an oncogene in glioblastoma and suggests that WISP1 may serve as a potential molecular marker and treatment target for glioblastoma.

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1	Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, Pekmezci M, Schwartzbaum JA, Turner MC, Walsh KM, et al: The epidemiology of glioma in adults: A 'state of the science' review. Neuro-oncol. 16:896–913. 2014. View Article : Google Scholar
2	Rao JS: Molecular mechanisms of glioma invasiveness: The role of proteases. Nat Rev Cancer. 3:489–501. 2003. View Article : Google Scholar : PubMed/NCBI
3	Gupta K and Salunke P: Molecular markers of glioma: An update on recent progress and perspectives. J Cancer Res Clin Oncol. 138:1971–1981. 2012. View Article : Google Scholar : PubMed/NCBI
4	Larjavaara S, Mäntylä R, Salminen T, Haapasalo H, Raitanen J, Jääskeläinen J and Auvinen A: Incidence of gliomas by anatomic location. Neuro-oncol. 9:319–325. 2007. View Article : Google Scholar : PubMed/NCBI
5	Martin S, Janouskova H and Dontenwill M: Integrins and p53 pathways in glioblastoma resistance to temozolomide. Front Oncol. 2:1572012. View Article : Google Scholar : PubMed/NCBI
6	Pegg AE: Repair of O(6)-alkylguanine by alkyltransferases. Mutat Res. 462:83–100. 2000. View Article : Google Scholar : PubMed/NCBI
7	Kleer CG: Dual roles of CCN proteins in breast cancer progression. J Cell Commun Signal. 10:217–222. 2016. View Article : Google Scholar : PubMed/NCBI
8	Holbourn KP, Acharya KR and Perbal B: The CCN family of proteins: Structure-function relationships. Trends Biochem Sci. 33:461–473. 2008. View Article : Google Scholar : PubMed/NCBI
9	Gurbuz I and Chiquet-Ehrismann R: CCN4/WISP1 (WNT1 inducible signaling pathway protein 1): A focus on its role in cancer. Int J Biochem Cell Biol. 62:142–146. 2015. View Article : Google Scholar : PubMed/NCBI
10	Wu J, Long Z, Cai H, Du C, Liu X, Yu S and Wang Y: High expression of WISP1 in colon cancer is associated with apoptosis, invasion and poor prognosis. Oncotarget. 7:49834–49847. 2016. View Article : Google Scholar : PubMed/NCBI
11	Chuang JY, Chen PC, Tsao CW, Chang AC, Lein MY, Lin CC, Wang SW, Lin CW and Tang CH: WISP-1 a novel angiogenic regulator of the CCN family promotes oral squamous cell carcinoma angiogenesis through VEGF-A expression. Oncotarget. 6:4239–4252. 2015. View Article : Google Scholar : PubMed/NCBI
12	Zhang H, Luo H, Hu Z, Peng J, Jiang Z, Song T, Wu B, Yue J, Zhou R, Xie R, et al: Targeting WISP1 to sensitize esophageal squamous cell carcinoma to irradiation. Oncotarget. 6:6218–6234. 2015. View Article : Google Scholar : PubMed/NCBI
13	Zhang H, Luo H, Jiang Z, Yue J, Hou Q, Xie R and Wu S: Fractionated irradiation-induced EMT-like phenotype conferred radioresistance in esophageal squamous cell carcinoma. J Radiat Res (Tokyo). 57:370–380. 2016. View Article : Google Scholar
14	Yu W, Song T, Shi L, Wang X, Jiang Z, Zhang H and Wu S: Targeted inhibition of WISP1 enhanced radiosensitivity in glioma cells. Zhonghua Yi Xue Za Zhi. 94:1507–1511. 2014.In Chinese. PubMed/NCBI
15	Minchenko OH, Kharkova AP, Minchenko DO and Karbovskyi LL: Effect of hypoxia on the expression of genes that encode some IGFBP and CCN proteins in U87 glioma cells depends on IRE1 signaling. Ukr Biochem J. 87:52–63. 2015. View Article : Google Scholar
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2 (−Delta Delta C (T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
17	Jun JI and Lau LF: Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov. 10:945–963. 2011. View Article : Google Scholar : PubMed/NCBI
18	Xie D, Nakachi K, Wang H, Elashoff R and Koeffler HP: Elevated levels of connective tissue growth factor, WISP-1, and CYR61 in primary breast cancers associated with more advanced features. Cancer Res. 61:8917–8923. 2001.PubMed/NCBI
19	Tian C, Zhou ZG, Meng WJ, Sun XF, Yu YY, Li L, Luo HZ, Yang L, Zhou B and Gu J: Overexpression of connective tissue growth factor WISP-1 in Chinese primary rectal cancer patients. World J Gastroenterol. 13:3878–3882. 2007. View Article : Google Scholar : PubMed/NCBI
20	Nagai Y, Watanabe M, Ishikawa S, Karashima R, Kurashige J, Iwagami S, Iwatsuki M, Baba Y, Imamura Y, Hayashi N, et al: Clinical significance of Wnt-induced secreted protein-1 (WISP-1/CCN4) in esophageal squamous cell carcinoma. Anticancer Res. 31:991–997. 2011.PubMed/NCBI
21	Shao H, Cai L, Grichnik JM, Livingstone AS, Velazquez OC and Liu ZJ: Activation of Notch1 signaling in stromal fibroblasts inhibits melanoma growth by upregulating WISP-1. Oncogene. 30:4316–4326. 2011. View Article : Google Scholar : PubMed/NCBI
22	Ono M, Inkson CA, Sonn R, Kilts TM, de Castro LF, Maeda A, Fisher LW, Robey PG, Berendsen AD, Li L, et al: WISP1/CCN4: A potential target for inhibiting prostate cancer growth and spread to bone. PLoS One. 8:e717092013. View Article : Google Scholar : PubMed/NCBI
23	De Salvo M, Maresca G, D'agnano I, Marchese R, Stigliano A, Gagliassi R, Brunetti E, Raza GH, De Paula U and Bucci B: Temozolomide induced c-Myc-mediated apoptosis via Akt signalling in MGMT expressing glioblastoma cells. Int J Radiat Biol. 87:518–533. 2011. View Article : Google Scholar : PubMed/NCBI
24	Nagasawa DT, Chow F, Yew A, Kim W, Cremer N and Yang I: Temozolomide and other potential agents for the treatment of glioblastoma multiforme. Neurosurg Clin N Am. 23:307–322. ix2012. View Article : Google Scholar : PubMed/NCBI
25	Stavrovskaya AA, Shushanov SS and Rybalkina EY: Problems of glioblastoma multiforme drug resistance. Biochemistry (Mosc). 81:91–100. 2016. View Article : Google Scholar
26	Luo H, Chen Z, Wang S, Zhang R, Qiu W, Zhao L, Peng C, Xu R, Chen W, Wang HW, et al: c-Myc-miR-29c-REV3L signalling pathway drives the acquisition of temozolomide resistance in glioblastoma. Brain. 138:3654–3672. 2015. View Article : Google Scholar : PubMed/NCBI
27	Nie E, Jin X, Wu W, Yu T, Zhou X, Zhi T, Shi Z, Zhang J, Liu N and You Y: BACH1 promotes temozolomide resistance in glioblastoma through antagonizing the function of p53. Sci Rep. 6:397432016. View Article : Google Scholar : PubMed/NCBI
28	Li DM and Feng YM: Signaling mechanism of cell adhesion molecules in breast cancer metastasis: Potential therapeutic targets. Breast Cancer Res Treat. 128:7–21. 2011. View Article : Google Scholar : PubMed/NCBI
29	Huan J, Wang L, Xing L, Qin X, Feng L, Pan X and Zhu L: Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2). Gene. 533:346–355. 2014. View Article : Google Scholar
30	Burotto M, Chiou VL, Lee JM and Kohn EC: The MAPK pathway across different malignancies: A new perspective. Cancer. 120:3446–3456. 2014. View Article : Google Scholar : PubMed/NCBI
31	Choe G, Park JK, Jouben-Steele L, Kremen TJ, Liau LM, Vinters HV, Cloughesy TF and Mischel PS: Active matrix metalloproteinase 9 expression is associated with primary glioblastoma subtype. Clin Cancer Res. 8:2894–2901. 2002.PubMed/NCBI
32	Zhang L, Liu H, Mu X, Cui J and Peng Z: Dysregulation of Fra1 expression by Wnt/β-catenin signalling promotes glioma aggressiveness through epithelial-mesenchymal transition. Biosci Rep. 37:372017. View Article : Google Scholar
33	Li H, Yuan X, Yan D, Li D, Guan F, Dong Y, Wang H, Liu X and Yang B: Long non-coding RNA MALAT1 decreases the sensitivity of resistant glioblastoma cell lines to temozolomide. Cell Physiol Biochem. 42:1192–1201. 2017. View Article : Google Scholar : PubMed/NCBI
34	Yang J, Zhang JN, Chen WL, Wang GS, Mao Q, Li SQ, Xiong WH, Lin YY, Ge JW, Li XX, et al: Effects of AQP5 gene silencing on proliferation, migration and apoptosis of human glioma cells through regulating EGFR/ERK/p38 MAPK signaling pathway. Oncotarget. 8:38444–38455. 2017.PubMed/NCBI
35	Zhao L: Hirudin inhibits cell growth via ERK/MAPK signaling in human glioma. Int J Clin Exp Med. 8:20983–20987. 2015.