High expression of citron kinase predicts poor prognosis of prostate cancer

Liu,Junnan; Dou,Jianguo; Wang,Wujiao; Liu,Hengchuan; Qin,Yunlang; Yang,Qixin; Jiang,Wencheng; Liang,Yong; Liu,Yuejiang; He,Jiang; Mai,Li; Li,Ying; Wang,Delin

doi:10.3892/ol.2020.11254

High expression of citron kinase predicts poor prognosis of prostate cancer

Authors:
- Junnan Liu
- Jianguo Dou
- Wujiao Wang
- Hengchuan Liu
- Yunlang Qin
- Qixin Yang
- Wencheng Jiang
- Yong Liang
- Yuejiang Liu
- Jiang He
- Li Mai
- Ying Li
- Delin Wang
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Affiliations: Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Urology, The People's Hospital of Dazu, Chongqing 400016, P.R. China, First Clinical Institute, Chongqing Medical University, Chongqing 400016, P.R. China, Department of Urology, The Zigong No. 4 People's Hospital, Zigong, Sichuan 643000, P.R. China, Department of Urology, The Zigong No. 1 People's Hospital, Zigong, Sichuan 643000, P.R. China, Gastroenterology and Neurology Center, University‑Town Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, College of Life Science, Chongqing Medical University, Chongqing 400016, P.R. China
Published online on: January 7, 2020 https://doi.org/10.3892/ol.2020.11254
Pages: 1815-1823
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Citron kinase (CIT) is a Rho‑effector protein kinase that is associated with several types of cancer. However, the role of CIT in prostate cancer (PCa) is unclear. The current study utilized microarray data obtained from The Cancer Genome Atlas, which was analyzed via Biometric Research Program array tools. Additionally, reverse transcription‑quantitative (RT‑q)PCR was performed to compare the mRNA expression of CIT in PCa tissue and in benign prostatic hyperplasia. The protein expression of CIT was detected in a consecutive cohort via immunochemistry and CIT was screened as a potential oncogene in PCa. The results of RT‑qPCR demonstrated that the mRNA expression of CIT was increased in PCa tissues. Furthermore, immunochemistry revealed that CIT protein expression was positively associated with age at diagnosis, Gleason grade, serum PSA, clinical T stage, risk group, lymph node invasion and metastasis. When compared with the low expression group, patients with a high CIT expression exhibited shorter survival rates, cancer specific mortalities (CSM) and biochemical recurrence (BCR). In addition, multivariate analysis revealed that CIT was a potential predictor of CSM and BCR. The results revealed that CIT is overexpressed during the malignant progression of PCa and may be a predictor of a poor patient prognosis.

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1	Siegel RL, Miller KD and Jemal A: Cancer Statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI
2	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
3	Pokorny MR, de Rooij M, Duncan E, Schröder FH, Parkinson R, Barentsz JO and Thompson LC: Prospective study of diagnostic accuracy comparing prostate cancer detection by trans rectal ultrasound-guided biopsy versus magnetic resonance (MR) imaging with subsequent MR-guided biopsy in men without previous prostate biopsies. Eur Urol. 66:22–29. 2014. View Article : Google Scholar : PubMed/NCBI
4	Zhang W, Vazquez L, Apperson M and Kennedy MB: Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus. J Neurosci. 19:96–108. 1999. View Article : Google Scholar : PubMed/NCBI
5	Fujiwara T, Bandi M, Nitta M, Ivanova EV, Bronson RT and Pellman D: Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature. 437:1043–1047. 2005. View Article : Google Scholar : PubMed/NCBI
6	Ganem NJ, Storchova Z and Pellman D: Tetraploidy, aneuploidy and cancer. Curr Opin Genet Dev. 17:157–162. 2007. View Article : Google Scholar : PubMed/NCBI
7	McKenzie C, Bassi ZI, Debski J, Gottardo M, Callaini G, Dadlez M and D'Avino PP: Cross-regulation between aurora B and citron kinase controls midbody architecture in cytokinesis. Open Biol. 6:1600192016. View Article : Google Scholar : PubMed/NCBI
8	D'Avino PP and Capalbo L: Regulation of midbody formation and function by mitotic kinases. Semin Cell Dev Biol. 53:57–63. 2016. View Article : Google Scholar : PubMed/NCBI
9	Gai M, Camera P, Dema A, Bianchi F, Berto G, Scarpa E, Germena G and Di Cunto F: Citron kinase controls abscission through RhoA and anillin. Mol Biol Cell. 22:3768–3778. 2011. View Article : Google Scholar : PubMed/NCBI
10	Yamashiro S, Totsukawa G, Yamakita Y, Sasaki Y, Madaule P, Ishizaki T, Narumiya S and Matsumura F: Citron kinase, a Rho-dependent kinase, induces di-phosphorylation of regulatory light chain of myosin II. Mol Biol Cell. 14:1745–1756. 2003. View Article : Google Scholar : PubMed/NCBI
11	Zhao Y and Simon R: BRB-ArrayTools data archive for human cancer gene expression: A unique and efficient data sharing resource. Cancer Inform. 6:9–15. 2008. View Article : Google Scholar : PubMed/NCBI
12	Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, et al: EAU-ESTRO-SIOG guidelines on prostate cancer Part 1: Screening, diagnosis, and local treatment with curative intent. Eur Urol. 71:618–629. 2017. View Article : Google Scholar : PubMed/NCBI
13	Yu L, Toriseva M, Tuomala M, Seikkula H, Elo T, Tuomela J, Kallajoki M, Mirtti T, Taimen P, Boström PJ, et al: Increased expression of fibroblast growth factor 13 in prostate cancer is associated with shortened time to biochemical recurrence after radical prostatectomy. Int J Cancer. 139:140–152. 2016. View Article : Google Scholar : PubMed/NCBI
14	Eble JN, Sauter G, Epstein JE and Sesterhenn IA: World Health Organization Classification of Tumours. Pathology and genetics of the urinary system and male genital organs. IARC Press; Lyon: 2004. pp. 159–215. 2004
15	Epstein JI, Allsbrook WC Jr, Amin MB and Egevad LL; ISUP Grading Committee, : The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 29:1228–1242. 2005. View Article : Google Scholar : PubMed/NCBI
16	Goktas S, Yilmaz MI, Caglar K, Sonmez A, Kilic S and Bedir S: Prostate cancer and adiponectin. Urology. 65:1168–1172. 2005. View Article : Google Scholar : PubMed/NCBI
17	Liu J, Xiao M, Li J, Wang D, He Y, He J, Gao F, Mai L, Li Y, Liang Y, et al: Activation of UPR signaling pathway is associated with the malignant progression and poor prognosis in prostate cancer. Prostate. 77:274–281. 2017. View Article : Google Scholar : PubMed/NCBI
18	Roudier MP, Winters BR, Coleman I, Lam HM, Zhang X, Coleman R, Chéry L, True LD, Higano CS, Montgomery B, et al: Characterizing the molecular features of ERG-Positive tumors in primary and castration resistant prostate cancer. Prostate. 76:810–822. 2016. View Article : Google Scholar : PubMed/NCBI
19	Sheng X, Li WB, Wang DL, Chen KH, Cao JJ, Luo Z, He J, Li MC, Liu WJ and Yu C: YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells. Mol Med Rep. 12:4867–4876. 2015. View Article : Google Scholar : PubMed/NCBI
20	Whitworth H, Bhadel S, Ivey M, Conaway M, Spencer A, Hernan R, Holemon H and Gioeli D: Identification of kinases regulating prostate cancer cell growth using an RNAi phenotypic screen. PLoS One. 7:e389502012. View Article : Google Scholar : PubMed/NCBI
21	Glotzer M: The molecular requirements for cytokinesis. Science. 307:1735–1739. 2005. View Article : Google Scholar : PubMed/NCBI
22	Boveri T: Concerning the origin of malignant tumors by Theodor Boveri. Translated and annotated by Henry Harris. J Cell Sci. 121:1–84. 2008. View Article : Google Scholar : PubMed/NCBI
23	Pihan GA, Purohit A, Wallace J, Malhotra R, Liotta L and Doxsey SJ: Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression. Cancer Res. 61:2212–2219. 2001.PubMed/NCBI
24	Yamamoto Y, Eguchi S, Junpei A, Nagao K, Sakano S, Furuya T, Oga A, Kawauchi S, Sasaki K and Matsuyama H: Intercellular centrosome number is correlated with the copy number of chromosomes in bladder cancer. Cancer Genet Cytogenet. 191:38–42. 2009. View Article : Google Scholar : PubMed/NCBI
25	Bassi ZI, Audusseau M, Riparbelli MG, Callaini G and D'Avino PP: Citron kinase controls a molecular network required for midbody formation in cytokinesis. Proc Natl Acad Sci USA. 110:9782–9787. 2013. View Article : Google Scholar : PubMed/NCBI
26	Madaule P, Eda M, Watanabe N, Fujisawa K, Matsuoka T, Bito H, Ishizaki T and Narumiya S: Role of citron kinase as a target of the small GTPase Rho in cytokinesis. Nature. 394:491–494. 1998. View Article : Google Scholar : PubMed/NCBI
27	Madhavan J, Mitra M, Mallikarjuna K, Pranav O, Srinivasan R, Nagpal A, Venkatesan P and Kumaramanickavel G: KIF14 and E2F3 mRNA expression in human retinoblastoma and its phenotype association. Mol Vis. 15:235–240. 2009.PubMed/NCBI
28	Zhang J, Yang PL and Gray NS: Targeting cancer with small molecule kinase inhibitors. Nat Rev Cancer. 9:28–39. 2009. View Article : Google Scholar : PubMed/NCBI
29	Garnett MJ and Marais R: Guilty as charged: B-RAF is a human oncogene. Cancer Cell. 6:313–319. 2004. View Article : Google Scholar : PubMed/NCBI
30	Mossé YP, Laudenslager M, Longo L, Cole KA, Wood A, Attiyeh EF, Laquaglia MJ, Sennett R, Lynch JE, Perri P, et al: Identification of ALK as a major familial neuroblastoma predisposition gene. Nature. 455:930–935. 2008. View Article : Google Scholar : PubMed/NCBI
31	Grise F, Bidaud A and Moreau V: Rho GTPases in hepatocellular carcinoma. Biochim Biophys Acta. 1795:137–151. 2009.PubMed/NCBI
32	Tang Y, Olufemi L, Wang MT and Nie D: Role of Rho GTPases in breast cancer. Front Biosci. 13:759–776. 2008. View Article : Google Scholar : PubMed/NCBI
33	Fu Y, Huang J, Wang KS, Zhang X and Han ZG: RNA interference targeting CITRON can significantly inhibit the proliferation of hepatocellular carcinoma cells. Mol Biol Rep. 38:693–702. 2011. View Article : Google Scholar : PubMed/NCBI
34	McKenzie C and D'Avino PP: Investigating cytokinesis failure as a strategy in cancer therapy. Oncotarget. 7:87323–87341. 2016. View Article : Google Scholar : PubMed/NCBI
35	Somlyo AV, Bradshaw D, Ramos S, Murphy C, Myers CE and Somlyo AP: Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells. Biochem Biophys Res Commun. 269:652–659. 2000. View Article : Google Scholar : PubMed/NCBI
36	Wu Y, He L, Zhang L, Chen J, Yi Z, Zhang J, Liu M and Pang X: Anacardic acid (6-pentadecylsalicylic acid) inhibits tumor angiogenesis by targeting Src/FAK/Rho GTPases signaling pathway. J Pharmacol Exp Ther. 339:403–411. 2011. View Article : Google Scholar : PubMed/NCBI
37	Porten SP, Whitson JM, Cowan JE, Cooperberg MR, Shinohara K, Perez N, Greene KL, Meng MV and Carroll PR: Changes in prostate cancer grade on serial biopsy in men undergoing active surveillance. J Clin Oncol. 29:2795–800. 2011. View Article : Google Scholar : PubMed/NCBI
38	Sharifi N, Gulley JL and Dahut WL: Androgen deprivation therapy for prostate cancer. JAMA. 294:238–244. 2005. View Article : Google Scholar : PubMed/NCBI
39	Kirby M, Hirst C and Crawford ED: Characterising the castration-resistant prostate cancer population: A systematic review. Int J Clin Pract. 65:1180–1192. 2011. View Article : Google Scholar : PubMed/NCBI
40	Puhr M, Hoefer J, Eigentler A, Ploner C, Handle F, Schaefer G, Kroon J, Leo A, Heidegger I, Eder I, et al: The Glucocorticoid receptor is a key player for prostate cancer cell survival and a target for improved Antiandrogen therapy. Clin Cancer Res. 24:927–938. 2018. View Article : Google Scholar : PubMed/NCBI
41	Arora VK, Schenkein E, Murali R, Subudhi SK, Wongvipat J, Balbas MD, Shah N, Cai L, Efstathiou E, Logothetis C, et al: Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade. Cell. 155:1309–1322. 2013. View Article : Google Scholar : PubMed/NCBI