Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

Li,Hui; You,Yanjie; Liu,Jianfeng

doi:10.3892/mmr.2018.9059

Cyclin‑dependent kinase 10 prevents glioma metastasis via modulation of Snail expression

Authors:
- Hui Li
- Yanjie You
- Jianfeng Liu
View Affiliations

Affiliations: Department of Neurosurgery, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Gastroenterology, Ningxia Hui Autonomous Region People's Hospital, Yinchuan, Ningxia Hui Autonomous Region 750021, P.R. China
Published online on: May 23, 2018 https://doi.org/10.3892/mmr.2018.9059
Pages: 1165-1170

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

Cyclin‑dependent kinase 10 (CDK10) has been indicated to be a candidate tumor suppressor in multiple cancer types. However, to the best of the authors' knowledge, its biological and regulatory functions in glioma have not been previously reported. In the present study, it was demonstrated that overexpression of CDK10 inhibited glioma cell proliferation and metastasis. By contrast, knockdown of CDK10 expression promoted these malignant phenotypes. It was additionally indicated that dysregulated CDK10 expression was associated with epithelial‑mesenchymal transition (EMT) and that it regulated the expression of zinc finger protein SNAI1 (Snail). Furthermore, silencing Snail expression rescued EMT phenotypes induced by CDK10 knockdown, suggesting that Snail may be involved in the mechanistic association between CDK10 and EMT. The present study illustrated that downregulation of CDK10 expression activated Snail‑driven EMT and consequently promoted glioma metastasis, suggesting that CDK10 may serve as a potential molecular target for glioma therapy.

View Figures

View References

1	Armstrong TS, Wen PY, Gilbert MR and Schiff D: Management of treatment-associated toxicites of anti-angiogenic therapy in patients with brain tumors. Neuro Oncol. 14:1203–1214. 2012. View Article : Google Scholar : PubMed/NCBI
2	Ohgaki H and Kleihues P: Epidemiology and etiology of gliomas. Acta Neuropathol. 109:93–108. 2005. View Article : Google Scholar : PubMed/NCBI
3	Wen PY and Kesari S: Malignant gliomas in adults. N Engl J Med. 359:492–507. 2019. View Article : Google Scholar
4	Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY and Olson JJ: Exciting new advances in neuro-oncology: The avenueto a cure for malignant glioma. CA Cancer J Clin. 60:166–193. 2010. View Article : Google Scholar : PubMed/NCBI
5	Nakada M, Nakada S, Demuth T, Tran NL, Hoelzinger DB and Berens ME: Molecular targets of glioma invasion. Cell Mol Life Sci. 64:458–478. 2007. View Article : Google Scholar : PubMed/NCBI
6	Graña X, Claudio PP, De Luca A, Sang N and Giordano A: PISSLRE, a human novel CDC2-related protein kinase. Oncogene. 9:2097–2103. 1994.PubMed/NCBI
7	Brambilla R and Draetta G: Molecular cloning of PISSLRE, a novel putative member of the cdk family of protein serine/threonine kinases. Oncogene. 9:3037–3041. 1994.PubMed/NCBI
8	Li S, MacLachlan TK, De Luca A, Claudio PP, Condorelli G and Giordano A: The cdc-2-related kinase, PISSLRE, is essential for cell growth and acts in G2 phase of the cell cycle. Cancer Res. 55:3992–3995. 1995.PubMed/NCBI
9	Iorns E, Turner NC, Elliott R, Syed N, Garrone O, Gasco M, Tutt AN, Crook T, Lord CJ and Ashworth A: Identification of CDK10 as an important determinant of resistance to endocrine therapy for breast cancer. Cancer Cell. 13:91–104. 2008. View Article : Google Scholar : PubMed/NCBI
10	You Y, Yang W, Wang Z, Zhu H, Li H, Lin C and Ran Y: Promoter hypermethylation contributes to the frequent suppression of the CDK10 gene in human nasopharyngeal carcinomas. Cell Oncol (Dordr). 36:323–331. 2013. View Article : Google Scholar : PubMed/NCBI
11	Yu JH, Zhong XY, Zhang WG, Wang ZD, Dong Q, Tai S, Li H and Cui YF: CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells. Oncol Rep. 27:1266–1276. 2012. View Article : Google Scholar : PubMed/NCBI
12	Zhong XY, Xu XX, Yu JH, Jiang GX, Yu Y, Tai S, Wang ZD and Cui YF: Clinical and biological significance of Cdk10 in hepatocellular carcinoma. Gene. 498:68–74. 2012. View Article : Google Scholar : PubMed/NCBI
13	You Y, Li H, Qin X, Zhang Y, Song W, Ran Y and Gao F: Decreased CDK10 expression correlates with lymph node metastasis and predicts poor outcome in breast cancer patients-a short report. Cell Oncol. 38:485–491. 2015. View Article : Google Scholar
14	Hong CQ, Zhang F, You YJ, Qiu WL, Giuliano AE, Cui XJ, Zhang GJ and Cui YK: Elevated C1orf63 expression is correlated with CDK10 and predicts better outcome for advanced breast cancers: A retrospective study. BMC Cancer. 15:5482015. View Article : Google Scholar : PubMed/NCBI
15	You Y, Liu J, Wang Z, Zhang Y, Ran Y, Guo X, Liu H and Wang H: The enhancement of radiosensitivity in human esophageal squamous cell carcinoma cells by zoledronic acid and its potential mechanism. Cytotechnology. 66:17–25. 2014. View Article : Google Scholar : PubMed/NCBI
16	You Y, Yang W, Qin X, Wang F, Li H, Lin C, Li W, Gu C, Zhang Y and Ran Y: ECRG4 acts as a tumor suppressor and as a determinant of chemotherapy resistance in human nasopharyngeal carcinoma. Cell Oncol. 38:205–214. 2015. View Article : Google Scholar
17	Lin C, Xin S, Qin X, Li H, Lin L and You Y: Zoledronic acid suppresses metastasis of esophageal squamous cell carcinoma cells through upregulating the tight junction protein occludin. Cytotechnology. 68:1233–1241. 2016. View Article : Google Scholar : PubMed/NCBI
18	Lee KH, Ahn EJ, Oh SJ, Kim O, Joo YE, Bae JA, Yoon S, Ryu HH, Jung S, Kim KK, et al: KITENIN promotes glioma invasiveness and progression, associated with the induction of EMT and stemness markers. Oncotarget. 6:3240–3253. 2015.PubMed/NCBI
19	Pang H, Zheng Y, Zhao Y, Xiu X and Wang J: miR-590-3p suppresses cancer cell migration, invasion and epithelial-mesenchymal transition in glioblastoma multiforme by targeting ZEB1 and ZEB2. Biochem Biophys Res Commun. 468:739–745. 2015. View Article : Google Scholar : PubMed/NCBI
20	Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI
21	Martin TA, Goyal A, Watkins G and Jiang WG: Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 12:488–496. 2005. View Article : Google Scholar : PubMed/NCBI
22	Nagaishi M, Paulus W, Brokinkel B, Vital A, Tanaka Y, Nakazato Y, Giangaspero F and Ohgaki H: Transcriptional factors for epithelial-mesenchymal transition are associated with mesenchymal differentiation in gliosarcoma. Brain Pathol. 22:670–676. 2012. View Article : Google Scholar : PubMed/NCBI
23	Myung J, Cho BK, Kim YS and Park SH: Snail and Cox-2 expressions are associated with WHO tumor grade and survival rate of patients with gliomas. Neuropathology. 30:224–231. 2010. View Article : Google Scholar : PubMed/NCBI
24	Xu T, Zhou M, Peng L, Kong S, Miao R, Shi Y, Sheng H and Li L: Upregulation of CD147 promotes cell invasion, epithelial-to-mesenchymal transition and activates MAPK/ERK signaling pathway in colorectal cancer. Int J Clin Exp Pathol. 7:7432–7441. 2014.PubMed/NCBI
25	Kimura Y, Shiozaki H, Hirao M, Maeno Y, Doki Y, Inoue M, Monden T, Ando-Akatsuka Y, Furuse M, Tsukita S and Monden M: Expression of occludin, tight-junction-associated protein, in human digestive tract. Am J Pathol. 151:45–54. 1997.PubMed/NCBI
26	Martin TA, Mansel RE and Jiang WG: Loss of occludin leads to the progression of human breast cancer. Int J Mol Med. 26:723–734. 2010. View Article : Google Scholar : PubMed/NCBI
27	Tobioka H, Isomura H, Kokai Y, Tokunaga Y, Yamaguchi J and Sawada N: Occludin expression decreases with the progression of human endometrial carcinoma. Hum Pathol. 35:159–164. 2004. View Article : Google Scholar : PubMed/NCBI
28	Wang Z, Wade P, Mandell KJ, Akyildiz A, Parkos CA, Mrsny RJ and Nusrat A: Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug. Oncogene. 26:1222–1230. 2007. View Article : Google Scholar : PubMed/NCBI