Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
January-2015 Volume 9 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
January-2015 Volume 9 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression

  • Authors:
    • Junji Ma
    • Junli Shi
    • Dongqiang Zhao
    • Lijuan Cheng
    • Wenbin  Wang
    • Fangfang Li
    • Xiaoyu Jiang
    • Huiqing Jiang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, Shijiazhuang, Hebei 050000, P.R. China, Department of Hepatobiliary Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Department of Biochemistry and Molecular Biology, Basic Medical College of Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA
  • Pages: 15-24
    |
    Published online on: October 24, 2014
       https://doi.org/10.3892/ol.2014.2637
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Cholangiocarcinoma cells originate in the biliary epithelium. The cells easily metastasize and cause relapse. The effect of Raf kinase inhibitor protein (RKIP) on the biological behavior of cholangiocarcinoma cells is not yet clear. In the present study, RKIP and cytokeratin 19 expression was detected in the extrahepatic tissues of cholangiocarcinoma patients by immunohistochemistry. RKIP small interfering (si)RNA or an RKIP‑overexpressing adenoviral vector were used to infect the human cholangiocarcinoma RBE cell line. RKIP protein or gene expression was analyzed by western blotting or reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), respectively. The cells were assayed for proliferation, apoptosis, invasion and migration. Matrix metalloproteinase 9 (MMP‑9) and tissue inhibitor of metalloproteinase 4 (TIMP‑4) mRNA was assayed by RT‑qPCR. RKIP expression was reduced in the extrahepatic cholangiocarcinoma tumor compared with the adjacent uninvolved peritumoral tissues. The current study revealed that RKIP expression was positively correlated with cell differentiation, but negatively correlated with lymph node or distant metastasis (P<0.05). RKIP siRNA treatment promoted RBE cell invasion, but RKIP overexpression prevented cell invasion. In the pDC316‑siRNA recombinant vector group, the cells migrated more quickly compared with the siRNA‑negative control group, and in the RKIP‑expressing adenoviral vector group, the cells migrated more slowly compared with the adenoviral negative control group. RKIP inhibited the invasive and metastatic ability of the cholangiocarcinoma cell line, RBE, by downregulating MMP‑9 and upregulating TIMP‑4 mRNA expression. RKIP is negatively associated with cholangiocarcinoma distant metastasis and prevents cholangiocarcinoma cell metastasis through downregulating MMP‑9 expression and upregulating TIMP‑4 expression.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Francis H, Alpini G and DeMorrow S: Recent advances in the regulation of cholangiocarcinoma growth. Am J Physiol Gastrointest Liver Physiol. 299:G1–G9. 2010. View Article : Google Scholar : PubMed/NCBI

2 

de Marsh RW, Alonzo M, Bajaj S, et al: Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part I: diagnosis-clinical staging and pathology. J Surg Oncol. 106:332–338. 2012. View Article : Google Scholar

3 

von Hahn T, Ciesek S, Wegener G, et al: Epidemiological trends in incidence and mortality of hepatobiliary cancers in Germany. Scand J Gastroenterol. 46:1092–1098. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Marzioni M, Saccomanno S, Candelaresi C, et al: Clinical implications of novel aspects of biliary pathophysiology. Dig Liver Dis. 42:238–244. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Ciombor KK and Goff LW: Current therapy and future directions in biliary tract malignancies. Curr Treat Options Oncol. 14:337–349. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Yeung K, Seitz T, Li S, et al: Suppression of Raf-1 kinase activity and MAP kinase signalling by RKIP. Nature. 401:173–177. 1999. View Article : Google Scholar : PubMed/NCBI

7 

Yeung KC, Rose DW, Dhillon AS, et al: Raf kinase inhibitor protein interacts with NF-kappaB-inducing kinase and TAK1 and inhibits NF-kappaB activation. Mol Cell Biol. 21:7207–7217. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Deiss K, Kisker C, Lohse MJ and Lorenz K: Raf kinase inhibitor protein (RKIP) dimer formation controls its target switch from Raf1 to G protein-coupled receptor kinase (GRK) 2. J Biol Chem. 287:23407–23417. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Chatterjee D, Bai Y, Wang Z, et al: RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis. J Biol Chem. 279:17515–17523. 2004. View Article : Google Scholar : PubMed/NCBI

10 

Moon A, Park JY, Sung JY, Park YK and Kim YW: Reduced expression of Raf-1 kinase inhibitory protein in renal cell carcinoma: a significant prognostic marker. Pathology. 44:534–539. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Yun J, Frankenberger CA, Kuo WL, et al: Signalling pathway for RKIP and Let-7 regulates and predicts metastatic breast cancer. EMBO J. 30:4500–4514. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Beshir AB, Ren G, Magpusao AN, et al: Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression. Cancer Lett. 299:137–149. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Ma J, Li F, Liu L, et al: Raf kinase inhibitor protein inhibits cell proliferation but promotes cell migration in rat hepatic stellate cells. Liver Int. 29:567–574. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Zhao D, Ma J, Shi J, et al: Raf kinase inhibitor protein inhibits esophageal cancer cell invasion through downregulation of matrix metalloproteinase expression. Oncol Rep. 30:304–312. 2013.PubMed/NCBI

15 

Birner P, Jesch B, Schultheis A and Schoppmann SF: RAF-kinase inhibitor protein (RKIP) downregulation in esophageal cancer and its metastases. Clin Exp Metastasis. 29:551–559. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Braconi C and Patel T: Cholangiocarcinoma: new insights into disease pathogenesis and biology. Infect Dis Clin North Am. 24:871–884. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Nathan H, Aloia TA, Vauthey JN, et al: A proposed staging system for intrahepatic cholangiocarcinoma. Ann Surg Oncol. 16:14–22. 2009. View Article : Google Scholar

18 

Ribero D, Nuzzo G, Amisano M, et al: Comparison of the prognostic accuracy of the sixth and seventh editions of the TNM classification for intrahepatic cholangiocarcinoma. HPB (Oxford). 13:198–205. 2011.

19 

Lorenz K, Lohse MJ and Quitterer U: Protein kinase C switches the Raf kinase inhibitor from Raf-1 to GRK-2. Nature. 426:574–579. 2003. View Article : Google Scholar : PubMed/NCBI

20 

Deiss K, Kisker C, Lohse MJ and Lorenz K: Raf kinase inhibitor protein (RKIP) dimer formation controls its target switch from Raf1 to G protein-coupled receptor kinase (GRK) 2. J Biol Chem. 287:23407–23417. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Escara-Wilke J, Yeung K and Keller ET: Raf kinase inhibitor protein (RKIP) in cancer. Cancer Metastasis Rev. 31:615–620. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K and Tsuneyoshi M: The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver. Mod Pathol. 9:901–909. 1996.PubMed/NCBI

23 

Kim HS, Lee SH, Won KY, et al: Expression of Raf-1 kinase inhibitory protein in carcinoma of the ampulla of Vater. Virchows Arch. 460:61–68. 2012. View Article : Google Scholar

24 

Al-Mulla F, Bitar MS, Taqi Z and Yeung KC: RKIP: much more than Raf kinase inhibitory protein. J Cell Physiol. 228:1688–1702. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Lódi C, Szabó E, Holczbauer A, et al: Claudin-4 differentiates biliary tract cancers from hepatocellular carcinomas. Mod Pathol. 19:460–469. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Thummarati P, Wijitburaphat S, Prasopthum A, et al: High level of urokinase plasminogen activator contributes to cholangiocarcinoma invasion and metastasis. World J Gastroenterol. 18:244–250. 2012. View Article : Google Scholar : PubMed/NCBI

27 

Park SY, Kim JH, Won HJ, Shin YM and Kim PN: Radiofrequency ablation of hepatic metastases after curative resection of extrahepatic cholangiocarcinoma. AJR Am J Roentgenol. 197:W1129–W1134. 2011. View Article : Google Scholar : PubMed/NCBI

28 

Wang Q, Tang H, Yin S and Dong C: Downregulation of microRNA-138 enhances the proliferation, migration and invasion of cholangiocarcinoma cells through the upregulation of RhoC/p-ERK/MMP-2/MMP-9. Oncol Rep. 29:2046–2052. 2013.PubMed/NCBI

29 

Leelawat K, Sakchinabut S, Narong S and Wannaprasert J: Detection of serum MMP-7 and MMP-9 in cholangiocarcinoma patients: evaluation of diagnostic accuracy. BMC Gastroenterol. 9:302009. View Article : Google Scholar : PubMed/NCBI

30 

French JJ, Midwinter MJ, Bennett MK, Manas DM and Charnley RM: A matrix metalloproteinase inhibitor to treat unresectable cholangiocarcinoma. HPB (Oxford). 7:289–291. 2005. View Article : Google Scholar

31 

Jo Chae K, Rha SY, Oh BK, et al: Expression of matrix metalloproteinase-2 and -9 and tissue inhibitor of metalloproteinase-1 and -2 in intraductal and nonintraductal growth type of cholangiocarcinoma. Am J Gastroenterol. 99:68–75. 2004. View Article : Google Scholar

32 

Selaru FM, Olaru AV, Kan T, et al: MicroRNA-21 is overexpressed in human cholangiocarcinoma and regulates programmed cell death 4 and tissue inhibitor of metalloproteinase 3. Hepatology. 49:1595–1601. 2009. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Ma J, Shi J, Zhao D, Cheng L, Wang W, Li F, Jiang X and Jiang H: Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression. Oncol Lett 9: 15-24, 2015.
APA
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F. ... Jiang, H. (2015). Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression. Oncology Letters, 9, 15-24. https://doi.org/10.3892/ol.2014.2637
MLA
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F., Jiang, X., Jiang, H."Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression". Oncology Letters 9.1 (2015): 15-24.
Chicago
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F., Jiang, X., Jiang, H."Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression". Oncology Letters 9, no. 1 (2015): 15-24. https://doi.org/10.3892/ol.2014.2637
Copy and paste a formatted citation
x
Spandidos Publications style
Ma J, Shi J, Zhao D, Cheng L, Wang W, Li F, Jiang X and Jiang H: Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression. Oncol Lett 9: 15-24, 2015.
APA
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F. ... Jiang, H. (2015). Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression. Oncology Letters, 9, 15-24. https://doi.org/10.3892/ol.2014.2637
MLA
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F., Jiang, X., Jiang, H."Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression". Oncology Letters 9.1 (2015): 15-24.
Chicago
Ma, J., Shi, J., Zhao, D., Cheng, L., Wang, W., Li, F., Jiang, X., Jiang, H."Raf kinase inhibitor protein inhibits cholangiocarcinoma cell metastasis by downregulating matrix metalloproteinase 9 and upregulating tissue inhibitor of metalloproteinase 4 expression". Oncology Letters 9, no. 1 (2015): 15-24. https://doi.org/10.3892/ol.2014.2637
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team