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Article

RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells

  • Authors:
    • Jun‑Feng Chen
    • Bi‑Xia Yu
    • Liang Ma
    • Xiu‑Yi Lv
    • Jun‑Hui Jiang
    • Qi Ma
  • View Affiliations / Copyright

    Affiliations: Translational Research Laboratory for Urology, The Key Laboratory of Ningbo, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315010, P.R. China
  • Pages: 6547-6554
    |
    Published online on: February 28, 2018
       https://doi.org/10.3892/ol.2018.8135
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Abstract

Tyrosine kinase receptor macrophage stimulating 1 receptor (MST1R, also known as RON) contributes to the transformation and malignant progression observed in epithelial cells. The purpose of the present study is to assess the value of RON as a potential target in bladder cancer (BC) therapeutics. The expression profile of RON in BC tissues and adjacent noncancerous tissues was detected via immunohistochemistry. The rate of positive RON expression differed significantly between bladder urothelial cancer tissues (54.7%) and paraneoplastic tissues (29.4%) (P<0.05). RON expression was positively associated with the number of tumors per patient, histological grading, pathological stage and distant metastasis (all P<0.05). Downregulation of RON expression using small interfering RNAs inhibited cell growth, cell migration and promoted cell apoptosis in the 5637 cell line. RON inhibition induced cell cycle arrest at the G1/S boundary following an increase of cyclin‑dependent kinase inhibitor 1B and cyclin‑dependent kinase inhibitor 1A, and a decrease of cyclin D1, cyclin D3 and cyclin‑dependent kinase 4 expression. Furthermore, knockdown of RON significantly blocked signal transduction, including downstream protein kinase B and mitogen‑activated protein kinase pathways. These results indicated that RON serves a notable role in BC and is a potential target of therapeutic intervention.
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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 

Martin-Doyle W and Kwiatkowski DJ: Molecular biology of bladder cancer. Hematol Oncol Clin North Am. 29:191–203. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Bellmunt J, Powles T and Vogelzang NJ: A review on the evolution of PD-1/PD-L1 immunotherapy for bladder cancer: The future is now. Cancer Treat Rev. 54:58–67. 2017. View Article : Google Scholar : PubMed/NCBI

4 

Pinto IG: Systemic therapy in bladder cancer. Indian J Urol. 33:118–126. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Mohammed AA, El-Tanni H, El-Khatib HM, Mirza AA, Mirza AA and Alturaifi TH: Urinary bladder cancer: Biomarkers and target therapy, new era for more attention. Oncol Rev. 10:3202016. View Article : Google Scholar : PubMed/NCBI

6 

Wang MH, Padhye SS, Guin S, Ma Q and Zhou YQ: Potential therapeutics specific to c-MET/RON receptor tyrosine kinases for molecular targeting in cancer therapy. Acta Pharmacol Sin. 31:1181–1188. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Park YL, Lee GH, Kim KY, Myung E, Kim JS, Myung DS, Park KJ, Cho SB, Lee WS, Jung YD, et al: Expression of RON in colorectal cancer and its relationships with tumor cell behavior and prognosis. Tumori. 98:652–662. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Feres KJ, Ischenko I and Hayman MJ: The RON receptor tyrosine kinase promotes MSP-independent cell spreading and survival in breast epithelial cells. Oncogene. 28:279–288. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Cheng HL, Liu HS, Lin YJ, Chen HH, Hsu PY, Chang TY, Ho CL, Tzai TS and Chow NH: Co-expression of RON and MET is a prognostic indicator for patients with transitional-cell carcinoma of the bladder. Br J Cancer. 92:1906–1914. 2005. View Article : Google Scholar : PubMed/NCBI

10 

Hsu PY, Liu HS, Cheng HL, Tzai TS, Guo HR, Ho CL and Chow NH: Collaboration of RON and epidermal growth factor receptor in human bladder carcinogenesis. J Urol. 176:2262–2267. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Chen JF, Yu BX, Yu R, Ma L, Lv XY, Cheng Y and Ma Q: Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis. Oncol Rep. 37:721–728. 2017. View Article : Google Scholar : PubMed/NCBI

12 

Yao HP, Zhou YQ, Zhang R and Wang MH: MSP-RON signaling in cancer: Pathogenesis and therapeutic potential. Nat Rev Cancer. 13:466–481. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Thomas RM, Toney K, Fenoglio-Preiser C, Revelo-Penafiel MP, Hingorani SR, Tuveson DA, Waltz SE and Lowy AM: The RON receptor tyrosine kinase mediates oncogenic phenotypes in pancreatic cancer cells and is increasingly expressed during pancreatic cancer progression. Cancer Res. 67:6075–6082. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Zarei O, Benvenuti S, Ustun-Alkan F, Hamzeh-Mivehroud M and Dastmalchi S: Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery. J Cancer Res Clin Oncol. 142:2429–2446. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Wang MH, Lee W, Luo YL, Weis MT and Yao HP: Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumorigenic phenotypes in thyroid cancer cells. J Pathol. 213:402–411. 2007. View Article : Google Scholar : PubMed/NCBI

16 

Wagh PK, Peace BE and Waltz SE: Met-related receptor tyrosine kinase Ron in tumor growth and metastasis. Adv Cancer Res. 100:1–33. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Camp ER, Liu W, Fan F, Yang A, Somcio R and Ellis LM: RON, a tyrosine kinase receptor involved in tumor progression and metastasis. Ann Surg Oncol. 12:273–281. 2005. View Article : Google Scholar : PubMed/NCBI

18 

Wang MH, Wang D and Chen YQ: Oncogenic and invasive potentials of human macrophage-stimulating protein receptor, the RON receptor tyrosine kinase. Carcinogenesis. 24:1291–1300. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Danilkovitch-Miagkova A: Oncogenic signaling pathways activated by RON receptor tyrosine kinase. Curr Cancer Drug Targets. 3:31–40. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Chung CY, Park YL, Song YA, Myung E, Kim KY, Lee GH, Ki HS, Park KJ, Cho SB, Lee WS, et al: Knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle arrest through the modulation of Akt/FoxO signaling in human colorectal cancer cells. Dig Dis Sci. 57:371–380. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Song YA, Park YL, Kim KY, Myung E, Chung CY, Cho SB, Lee WS, Jung YD, Kweon SS and Joo YE: RON is associated with tumor progression via the inhibition of apoptosis and cell cycle arrest in human gastric cancer. Pathol Int. 62:127–136. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Cho SB, Park YL, Song YA, Kim KY, Lee GH, Cho DH, Myung DS, Park KJ, Lee WS, Chung IJ, et al: Small interfering RNA-directed targeting of RON alters invasive and oncogenic phenotypes of human hepatocellular carcinoma cells. Oncol Rep. 26:1581–1586. 2011.PubMed/NCBI

23 

Morgan DO: Cyclin-dependent kinases: Engines, clocks, and microprocessors. Annu Rev Cell Dev Biol. 13:261–291. 1997. View Article : Google Scholar : PubMed/NCBI

24 

Murray AW and Marks D: Can sequencing shed light on cell cycling? Nature. 409:844–846. 2001. View Article : Google Scholar : PubMed/NCBI

25 

Connell-Crowley L, Elledge SJ and Harper JW: G1 cyclin-dependent kinases are sufficient to initiate DNA synthesis in quiescent human fibroblasts. Curr Biol. 8:65–68. 1998. View Article : Google Scholar : PubMed/NCBI

26 

Vermeulen K, van Bockstaele DR and Berneman ZN: The cell cycle: A review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif. 36:131–149. 2003. View Article : Google Scholar : PubMed/NCBI

27 

Huang Y, Hu J, Zheng J, Li J, Wei T, Zheng Z and Cheng Y: Down-regulation of the PI3K/Akt signaling pathway and induction of apoptosis in CA46 Burkitt lymphoma cells by baicalin. J Exp Clin Cancer Res. 31:482012. View Article : Google Scholar : PubMed/NCBI

28 

Wang MH, Zhang R, Zhou YQ and Yao HP: Pathogenesis of RON receptor tyrosine kinase in cancer cells: Activation mechanism, functional crosstalk, and signaling addiction. J Biomed Res. 27:345–356. 2013.PubMed/NCBI

29 

Lu Y, Yao HP and Wang MH: Multiple variants of the RON receptor tyrosine kinase: Biochemical properties, tumorigenic activities, and potential drug targets. Cancer Lett. 257:157–164. 2007. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chen JF, Yu BX, Ma L, Lv XY, Jiang JH and Ma Q: RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells. Oncol Lett 15: 6547-6554, 2018.
APA
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., & Ma, Q. (2018). RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells. Oncology Letters, 15, 6547-6554. https://doi.org/10.3892/ol.2018.8135
MLA
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., Ma, Q."RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells". Oncology Letters 15.5 (2018): 6547-6554.
Chicago
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., Ma, Q."RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells". Oncology Letters 15, no. 5 (2018): 6547-6554. https://doi.org/10.3892/ol.2018.8135
Copy and paste a formatted citation
x
Spandidos Publications style
Chen JF, Yu BX, Ma L, Lv XY, Jiang JH and Ma Q: RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells. Oncol Lett 15: 6547-6554, 2018.
APA
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., & Ma, Q. (2018). RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells. Oncology Letters, 15, 6547-6554. https://doi.org/10.3892/ol.2018.8135
MLA
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., Ma, Q."RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells". Oncology Letters 15.5 (2018): 6547-6554.
Chicago
Chen, J., Yu, B., Ma, L., Lv, X., Jiang, J., Ma, Q."RON is overexpressed in bladder cancer and contributes to tumorigenic phenotypes in 5637 cells". Oncology Letters 15, no. 5 (2018): 6547-6554. https://doi.org/10.3892/ol.2018.8135
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