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BioMed Research International
Volume 2015, Article ID 148651, 8 pages
http://dx.doi.org/10.1155/2015/148651
Research Article

Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth

1Laboratory for Biochemical Neuroendocrinology, Department of Human Genetics, KU Leuven, Herestraat 49, 3000 Leuven, Belgium
2Laboratory of Biochemical Neuroendocrinology, Institut de Recherches Cliniques de Montréal, Montreal, QC, Canada H2W 1R7
3Angiogenesis Laboratory, Université Bordeaux I, 33400 Talence, France
4INSERM, UMR 1029, 33400 Talence, France

Received 11 September 2014; Revised 30 December 2014; Accepted 11 January 2015

Academic Editor: Athanasios G. Pallis

Copyright © 2015 Jeroen Declercq et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. W. M. Creemers and A.-M. Khatib, “Knock-out mouse models of proprotein convertases: unique functions or redundancy?” Frontiers in Bioscience, vol. 13, no. 13, pp. 4960–4971, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. N. G. Seidah and A. Prat, “The biology and therapeutic targeting of the proprotein convertases,” Nature Reviews Drug Discovery, vol. 11, no. 5, pp. 367–383, 2012. View at Publisher · View at Google Scholar · View at Scopus
  3. D. E. Bassi, H. Mahloogi, L. Al-Saleem, R. L. De Cicco, J. A. Ridge, and A. J. P. Klein-Szanto, “Elevated furin expression in aggressive human head and neck tumors and tumor cell lines,” Molecular Carcinogenesis, vol. 31, no. 4, pp. 224–232, 2001. View at Publisher · View at Google Scholar · View at Scopus
  4. M. Cheng, P. Watson, J. Paterson, N. Seidah, M. Chrétien, and R. P. Shiu, “Proprotein convertase gene expression in human breast cancer,” International Journal of Cancer, vol. 71, no. 6, pp. 966–971, 1997. View at Publisher · View at Google Scholar
  5. M. Mbikay, F. Sirois, J. Yao, N. G. Seidah, and M. Chrétien, “Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumours,” British Journal of Cancer, vol. 75, no. 10, pp. 1509–1514, 1997. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Mercapide, R. L. De Cicco, D. E. Bassi, J. S. Castresana, G. Thomas, and A. J. P. Klein-Szanto, “Inhibition of furin-mediated processing results in suppression of astrocytoma cell growth and invasiveness,” Clinical Cancer Research, vol. 8, no. 6, pp. 1740–1746, 2002. View at Google Scholar · View at Scopus
  7. R. E. Page, A. J. P. Klein-Szanto, S. Litwin et al., “Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer,” Cellular Oncology, vol. 29, no. 4, pp. 289–299, 2007. View at Google Scholar · View at Scopus
  8. J. A. Schalken, A. J. M. Roebroek, P. P. C. A. Oomen et al., “fur gene expression as a discriminating marker for small cell and nonsmall cell lung carcinomas,” The Journal of Clinical Investigation, vol. 80, no. 6, pp. 1545–1549, 1987. View at Publisher · View at Google Scholar · View at Scopus
  9. J. Fu, D. E. Bassi, J. Zhang et al., “Enhanced UV-induced skin carcinogenesis in transgenic mice overexpressing proprotein convertases,” Neoplasia, vol. 15, no. 2, pp. 169–179, 2013. View at Google Scholar · View at Scopus
  10. R. Longuespee, F. Couture, C. Levesque et al., “Implications of proprotein convertases in ovarian cancer cell proliferation and tumor progression: insights for PACE4 as a therapeutic target,” Translational Oncology, vol. 7, no. 3, pp. 410–419, 2014. View at Publisher · View at Google Scholar
  11. J. W. M. Creemers, A. J. M. Roebroek, and W. J. M. Van de Ven, “Expression in human lung tumor cells of the proprotein processing enzyme PC1/PC3 Cloning and primary sequence of a 5 kb cDNA,” FEBS Letters, vol. 300, no. 1, pp. 82–88, 1992. View at Publisher · View at Google Scholar · View at Scopus
  12. N. Scamuffa, G. Siegfried, Y. Bontemps et al., “Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells,” Journal of Clinical Investigation, vol. 118, no. 1, pp. 352–363, 2008. View at Publisher · View at Google Scholar · View at Scopus
  13. R. L. De Cicco, D. E. Bassi, S. Zucker, N. G. Seidah, and A. J. P. Klein-Szanto, “Human carcinoma cell growth and invasiveness is impaired by the propeptide of the ubiquitous proprotein convertase furin,” Cancer Research, vol. 65, no. 10, pp. 4162–4171, 2005. View at Publisher · View at Google Scholar · View at Scopus
  14. D. E. Bassi, H. Mahloogi, R. L. de Cicco, and A. Klein-Szanto, “Increased furin activity enhances the malignant phenotype of human head and neck cancer cells,” The American Journal of Pathology, vol. 162, no. 2, pp. 439–447, 2003. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Fu, D. E. Bassi, J. Zhang, T. Li, E. Nicolas, and A. J. P. Klein-Szanto, “Transgenic overexpression of the proprotein convertase furin enhances skin tumor growth,” Neoplasia, vol. 14, no. 4, pp. 271–282, 2012. View at Publisher · View at Google Scholar · View at Scopus
  16. L. De Vos, J. Declercq, G. G. Rosas et al., “MMTV-cre-mediated fur inactivation concomitant with PLAG1 proto-oncogene activation delays salivary gland tumorigenesis in mice,” International Journal of Oncology, vol. 32, no. 5, pp. 1073–1083, 2008. View at Google Scholar · View at Scopus
  17. J. Declercq, I. Skaland, F. Van Dyck et al., “Adenomyoepitheliomatous lesions of the mammary glands in transgenic mice with targeted PLAG1 overexpression,” International Journal of Cancer, vol. 123, no. 7, pp. 1593–1600, 2008. View at Publisher · View at Google Scholar · View at Scopus
  18. J. Declercq, F. Van Dyck, B. Van Damme, and W. J. M. Van De Ven, “Upregulation of Igf and Wnt signalling associated genes in pleomorphic adenomas of the salivary glands in PLAG1 transgenic mice,” International Journal of Oncology, vol. 32, no. 5, pp. 1041–1047, 2008. View at Google Scholar · View at Scopus
  19. N. Scamuffa, F. Sfaxi, J. Ma et al., “Prodomain of the proprotein convertase subtilisin/kexin Furin (ppFurin) protects from tumor progression and metastasis,” Carcinogenesis, vol. 35, no. 3, pp. 528–536, 2014. View at Publisher · View at Google Scholar
  20. E. D. Anderson, L. Thomas, J. S. Hayflick, and G. Thomas, “Inhibition of HIV-1 gp160-dependent membrane fusion by a furin-directed alpha 1-antitrypsin variant,” The Journal of Biological Chemistry, vol. 268, no. 33, pp. 24887–24891, 1993. View at Google Scholar · View at Scopus
  21. G. L. Becker, F. Sielaff, M. E. Than et al., “Potent inhibitors of furin and furin-like proprotein convertases containing decarboxylated P1 arginine mimetics,” Journal of Medicinal Chemistry, vol. 53, no. 3, pp. 1067–1075, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. X. Sun, R. Essalmani, N. G. Seidah, and A. Prat, “The proprotein convertase PC5/6 is protective against intestinal tumorigenesis: in vivo mouse model,” Molecular Cancer, vol. 8, article 73, 2009. View at Publisher · View at Google Scholar · View at Scopus
  23. J. J. Zhu, J. Declercq, B. Roucourt et al., “Generation and characterization of non-competitive furin-inhibiting nanobodies,” Biochemical Journal, vol. 448, no. 1, pp. 73–82, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. K. Hada, K. Isshiki, S. Matsuda, K. Yuasa, and A. Tsuji, “Engineering of alpha 1-antitrypsin variants with improved specificity for the proprotein convertase furin using site-directed random mutagenesis,” Protein Engineering, Design and Selection, vol. 26, no. 2, pp. 123–131, 2013. View at Publisher · View at Google Scholar · View at Scopus
  25. D. D. Rao, P. B. Maples, N. Senzer et al., “Enhanced target gene knockdown by a bifunctional shRNA: a novel approach of RNA interference,” Cancer Gene Therapy, vol. 17, no. 11, pp. 780–791, 2010. View at Publisher · View at Google Scholar · View at Scopus
  26. C. de Martel, J. Ferlay, S. Franceschi et al., “Global burden of cancers attributable to infections in 2008: a review and synthetic analysis,” The Lancet Oncology, vol. 13, no. 6, pp. 607–615, 2012. View at Publisher · View at Google Scholar · View at Scopus
  27. R.-N. Chen, Y.-H. Huang, Y.-C. Lin et al., “Thyroid hormone promotes cell invasion through activation of furin expression in human hepatoma cell lines,” Endocrinology, vol. 149, no. 8, pp. 3817–3831, 2008. View at Publisher · View at Google Scholar · View at Scopus
  28. Y.-H. Huang, K.-H. Lin, C.-H. Liao, M.-W. Lai, Y.-H. Tseng, and C.-T. Yeh, “Furin overexpression suppresses tumor growth and predicts a better postoperative disease-free survival in hepatocellular carcinoma,” PLoS ONE, vol. 7, no. 7, Article ID e40738, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. A. J. M. Roebroek, N. A. Taylor, E. Louagie et al., “Limited redundancy of the proprotein convertase furin in mouse liver,” The Journal of Biological Chemistry, vol. 279, no. 51, pp. 53442–53450, 2004. View at Publisher · View at Google Scholar · View at Scopus
  30. E. Dupuy, P. Hainaud, A. Villemain et al., “Tumoral angiogenesis and tissue factor expression during hepatocellular carcinoma progression in a transgenic mouse model,” Journal of Hepatology, vol. 38, no. 6, pp. 793–802, 2003. View at Publisher · View at Google Scholar · View at Scopus
  31. C. Postic, M. Shiota, K. D. Niswender et al., “Dual roles for glucokinase in glucose homeostasis as determined by liver and pancreatic β cell-specific gene knock-outs using Cre recombinase,” The Journal of Biological Chemistry, vol. 274, no. 1, pp. 305–315, 1999. View at Publisher · View at Google Scholar · View at Scopus
  32. K. J. Livak and T. D. Schmittgen, “Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method,” Methods, vol. 25, no. 4, pp. 402–408, 2001. View at Publisher · View at Google Scholar · View at Scopus
  33. F. van Dyck, J. Declercq, C. V. Braem, and W. J. M. van de Ven, “PLAG1, the prototype of the PLAG gene family: versatility in tumour development (review),” International Journal of Oncology, vol. 30, no. 4, pp. 765–774, 2007. View at Google Scholar · View at Scopus
  34. M. T. Sáenz Robles and J. M. Pipas, “T antigen transgenic mouse models,” Seminars in Cancer Biology, vol. 19, no. 4, pp. 229–235, 2009. View at Publisher · View at Google Scholar · View at Scopus