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Article

A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway

  • Authors:
    • Bingshan Liu
    • Guojun Li
    • Xiao Wang
    • Yang Liu
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics, Huaihe Hospital, Henan University, Kaifeng, Henan 475001, P.R. China
  • Pages: 1033-1038
    |
    Published online on: January 29, 2014
       https://doi.org/10.3892/ol.2014.1839
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Abstract

This study aimed to explore the exact mechanism of the effect of a furin inhibitor on the migration and invasion of MG‑63 and Saos‑2 osteosarcoma cells. MG‑63 and Saos‑2 osteosarcoma cells were treated with regular culture medium in the presence or absence of 480 nM α1‑antitrypsin Portland (α1‑PDX). Wound‑healing and Transwell assays were used for the detection of the effects of α1‑PDX on MG‑63 and Saos‑2 osteosarcoma cell migration and invasion. Western blot analysis and reverse transcription‑polymerase chain reaction were performed to detect the expression levels of membrane type I matrix metalloproteinase (MT1‑MMP), Wnt and β‑catenin. A chromatin immunoprecipitation assay was used for detection of the levels of MT1‑MMP gene transcription activity. The results showed that α1‑PDX treatment significantly reduced the migration and invasion ability of the cells. Notably, the expression levels of MT1‑MMP decreased evidently upon α1‑PDX treatment, paralleled with reductions in the expression levels of Wnt and β‑catenin. Further analysis of the transcriptional activity of MT1‑MMP revealed that the α1‑PDX‑induced downregulation of the levels of MT1‑MMP was mediated by the Wnt signaling pathway. These data suggest that α1‑PDX plays a vital role in inhibiting MG‑63 and Saos‑2 osteosarcoma cell migration and invasion by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway.
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1 

Gawlik K, Shiryaev SA and Zhu W: Autocatalytic activation of the furin zymogen requires removal of the emerging enzyme’s N-terminus from the active site. PLoS One. 4:e50312009.PubMed/NCBI

2 

Vey M, Schäfer W, Berghöfer S, Klenk HD and Garten W: Maturation of the trans-Golgi network protease furin: compartmentalization of propeptide removal, substrate cleavage, and COOH-terminal truncation. J Cell Biol. 127:1829–1842. 1994. View Article : Google Scholar

3 

Creemers JW, Vey M, Schäfer W, Ayoubi TA, Roebroek AJ, Klenk HD, Garten W and Van de Ven WJ: Endoproteolytic cleavage of its propeptide is a prerequisite for efficient transport of furin out of the endoplasmic reticulum. J Biol Chem. 270:2695–2702. 1995. View Article : Google Scholar

4 

Anderson ED, VanSlyke JK, Thulin CD, Jean F and Thomas G: Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage. EMBO J. 16:1508–1518. 1997. View Article : Google Scholar

5 

Molloy SS, Thomas L, VanSlyke JK, et al: Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface. EMBO J. 13:18–33. 1994.PubMed/NCBI

6 

Fujisawa T, Kamimura H, Hosaka M, et al: Functional localization of proprotein-convertase furin and its substrate TGFbeta in EGF receptor-expressing gastric chief cells. Growth Factors. 22:51–59. 2004. View Article : Google Scholar

7 

Louagie E, Taylor NA, Flamez D, et al: Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate. Proc Natl Acad Sci USA. 105:12319–12324. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Yana I and Weiss SJ: Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases. Mol Biol Cell. 11:2387–2401. 2000. View Article : Google Scholar : PubMed/NCBI

9 

Dangi-Garimella S, Krantz SB, Barron MR, et al: Three-dimensional collagen I promotes gemcitabine resistance in pancreatic cancer through MT1-MMP-mediated expression of HMGA2. Cancer Res. 71:1019–1028. 2011. View Article : Google Scholar

10 

López de Cicco R, Bassi DE, Zucker S, et al: Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin. Cancer Res. 65:4162–4171. 2005.PubMed/NCBI

11 

Thomas G: Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 3:753–766. 2002. View Article : Google Scholar : PubMed/NCBI

12 

Nusse R and Varmus HE: Wnt genes. Cell. 69:1073–1087. 1992. View Article : Google Scholar : PubMed/NCBI

13 

McMahon AP, Gavin BJ, Parr B, et al: The Wnt family of cell signalling molecules in postimplantation development of the mouse. Ciba Found Symp. 165:199–218. 1992.PubMed/NCBI

14 

Polakis P: The many ways of Wnt in cancer. Curr Opin Genet Dev. 17:45–51. 2007. View Article : Google Scholar : PubMed/NCBI

15 

Smalley MJ and Dale TC: Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev. 18:215–230. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Wang Y: Wnt/Planar cell polarity signaling: a new paradigm for cancer therapy. Mol Cancer Ther. 8:2103–2109. 2009. View Article : Google Scholar : PubMed/NCBI

17 

Katoh M: WNT/PCP signaling pathway and human cancer (review). Oncol Rep. 14:1583–1588. 2005.PubMed/NCBI

18 

Hecht A, Vleminckx K, Stemmler MP, et al: The p300/CBP acetyltransferases function as transcriptional coactivators of beta-catenin in vertebrates. EMBO J. 19:1839–1850. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Takemaru KI and Moon RT: The transcriptional coactivator CBP interacts with beta-catenin to activate gene expression. J Cell Biol. 149:249–254. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Inagawa S, Itabashi M, Adachi S, et al: Expression and prognostic roles of beta-catenin in hepatocellular carcinoma: correlation with tumor progression and postoperative survival. Clin Cancer Res. 8:450–456. 2002.

21 

Wong CM, Fan ST and Ng IO: beta-Catenin mutation and overexpression in hepatocellular carcinoma: clinicopathologic and prognostic significance. Cancer. 92:136–145. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Pulyaeva H, Bueno J, Polette M, Birembaut P, Sato H, Seiki M and Thompson EW: MT1-MMP correlates with MMP-2 activation potential seen after epithelial to mesenchymal transition in human breast carcinoma cells. Clin Exp Metastasis. 15:111–120. 1997. View Article : Google Scholar

23 

Takahashi M, Tsunoda T, Seiki M, Nakamura Y and Furukawa Y: Identification of membrane-type matrix metalloproteinase-1 as a target of the beta-catenin/Tcf4 complex in human colorectal cancers. Oncogene. 21:5861–5867. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Kessenbrock K, Plaks V and Werb Z: Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 141:52–67. 2010. View Article : Google Scholar : PubMed/NCBI

25 

Itoh Y and Seiki M: MT1-MMP: a potent modifier of pericellular microenvironment. J Cell Physiol. 206:1–8. 2006. View Article : Google Scholar : PubMed/NCBI

26 

Kajita M, Itoh Y, Chiba T, Mori H, Okada A, Kinoh H and Seiki M: Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. J Cell Biol. 153:893–904. 2001. View Article : Google Scholar : PubMed/NCBI

27 

Deryugina EI, Ratnikov BI, Postnova TI, Rozanov DV and Strongin AY: Processing of integrin alpha(v) subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin and enhances tyrosine phosphorylation of focal adhesion kinase. J Biol Chem. 277:9749–9756. 2002. View Article : Google Scholar

28 

Overall CM: Molecular determinants of metalloproteinase substrate specificity: matrix metalloproteinase substrate binding domains, modules, and exosites. Mol Biotechnol. 22:51–86. 2002. View Article : Google Scholar

29 

Harada T, Arii S, Mise M, Imamura T, Higashitsuji H, et al: Membrane-type matrix metalloproteinase-1(MT1-MMP) gene is overexpressed in highly invasive hepatocellular carcinomas. J Hepatol. 28:231–239. 1998. View Article : Google Scholar

30 

Arii S, Mise M, Harada T, Furutani M, Ishigami S, Niwano M, et al: Overexpression of matrix metalloproteinase-9 gene in hepatocellular carcinoma with invasive potential. Hepatology. 24:316–322. 1996. View Article : Google Scholar : PubMed/NCBI

31 

Nagase H, Visse R and Murphy G: Structure and function of matrix metalloproteinases and TIMPs. Cardiovasc Res. 69:562–573. 2006. View Article : Google Scholar : PubMed/NCBI

32 

Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2:161–174. 2002. View Article : Google Scholar : PubMed/NCBI

33 

Kähäri VM and Saarialho-Kere U: Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med. 31:34–45. 1999.PubMed/NCBI

34 

Sato H, Takino T, Okada Y, Cao J, Shinagaw A, Yamamoto E and Seiki M: A matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 370:61–65. 1994. View Article : Google Scholar : PubMed/NCBI

35 

Sounni NE and Noel A: Membrane type-matrix metalloproteinases and tumor progression. Biochimie. 87:329–342. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Sato H, Takino T and Miyamori H: Roles of membrane-type matrix metalloproteinase-1 in tumor invasion and metastasis. Cancer Sci. 96:212–217. 2005. View Article : Google Scholar : PubMed/NCBI

37 

Seiki M: Membrane-type 1 matrix metalloproteinase: a key enzyme for tumor invasion. Cancer Lett. 194:1–11. 2003. View Article : Google Scholar : PubMed/NCBI

38 

Holmbeck K, Bianco P, Yamada S and Birkedal-Hansen H: MT1-MMP: a tethered collagenase. J Cell Physiol. 200:11–19. 2004. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu B, Li G, Wang X and Liu Y: A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway. Oncol Lett 7: 1033-1038, 2014.
APA
Liu, B., Li, G., Wang, X., & Liu, Y. (2014). A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway. Oncology Letters, 7, 1033-1038. https://doi.org/10.3892/ol.2014.1839
MLA
Liu, B., Li, G., Wang, X., Liu, Y."A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway". Oncology Letters 7.4 (2014): 1033-1038.
Chicago
Liu, B., Li, G., Wang, X., Liu, Y."A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway". Oncology Letters 7, no. 4 (2014): 1033-1038. https://doi.org/10.3892/ol.2014.1839
Copy and paste a formatted citation
x
Spandidos Publications style
Liu B, Li G, Wang X and Liu Y: A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway. Oncol Lett 7: 1033-1038, 2014.
APA
Liu, B., Li, G., Wang, X., & Liu, Y. (2014). A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway. Oncology Letters, 7, 1033-1038. https://doi.org/10.3892/ol.2014.1839
MLA
Liu, B., Li, G., Wang, X., Liu, Y."A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway". Oncology Letters 7.4 (2014): 1033-1038.
Chicago
Liu, B., Li, G., Wang, X., Liu, Y."A furin inhibitor downregulates osteosarcoma cell migration by downregulating the expression levels of MT1‑MMP via the Wnt signaling pathway". Oncology Letters 7, no. 4 (2014): 1033-1038. https://doi.org/10.3892/ol.2014.1839
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