Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth

Molecular Carcinogenesis

Volumn 56, Issue 3, 2017, Pages 1182-1188

  Bassi, Daniel E ^a   Zhang, Jirong ^a   Renner, Catherine ^a   Klein Szanto, Andres J ^a  

^a FOX CHASE CANCER CENTER   (United States)

Author keywords

furin; IGF 1R; lung cancer; PCSKC3; proprotein convertases; tumor development

Indexed keywords

ANTINEOPLASTIC AGENT; DECANOYL ARGINYLVALYLLYSYLARGININE CHLOROMETHYLKETONE; FURIN; SERINE PROTEINASE INHIBITOR; SOMATOMEDIN C; UNCLASSIFIED DRUG; ENZYME INHIBITOR; FURIN PROTEIN, HUMAN; SERINE PROTEINASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CELL CYCLE G0 PHASE; CELL CYCLE M PHASE; CELL PROLIFERATION; CHRONOPHARMACOLOGY; CONTROLLED STUDY; DRUG EFFICACY; DRUG MECHANISM; DRUG TARGETING; GENE OVEREXPRESSION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTRACELLULAR SIGNALING; LONG TERM CARE; LUNG CANCER CELL LINE; MITOSIS INDEX; MOUSE; NON SMALL CELL LUNG CANCER; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROCESSING; SHORT COURSE THERAPY; TREATMENT DURATION; TUMOR XENOGRAFT; A-549 CELL LINE; ANIMAL; CANCER TRANSPLANTATION; DRUG EFFECTS; GENE EXPRESSION REGULATION; LUNG TUMOR; METABOLISM; TUMOR CELL LINE; UPREGULATION;

A549 CELLS; ANIMALS; CARCINOMA, NON-SMALL-CELL LUNG; CELL LINE, TUMOR; CELL PROLIFERATION; ENZYME INHIBITORS; FURIN; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; IN VITRO TECHNIQUES; LUNG NEOPLASMS; MICE; NEOPLASM TRANSPLANTATION; PROPROTEIN CONVERTASES; UP-REGULATION;

EID: 84988649922     PISSN: 08991987     EISSN: 10982744     Source Type: Journal    
DOI: 10.1002/mc.22550     Document Type: Article

References (34)

1. Bassi DE, Fu J, Lopez de Cicco R, Klein-Szanto AJP. Proprotein convertases: “Master Switches” in the regulation of tumor growth and progression. Mol Carcinog 2005; 44:151–161.
2. Seidah NG, Sadr MS, Chrétien M, Mbikay M. The multifaceted proprotein convertases: Their unique, redundant, complementary, and opposite functions. J Biol Chem 2013; 288:21473–21481.
3. Scamuffa N, Calvo F, Chretien M, et al. Proprotein convertases: Lessons from knockouts. Faseb J 2006; 20:1954–1963.
4. Yana I, Weiss SJ. Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases. Mol Biol Cell 2000; 11:2387–2401.
5. Taylor NA, Van De Ven WJ, Creemers JW. Curbing activation: Proprotein convertases in homeostasis and pathology. Faseb J 2003; 17:1215–1227.
6. Thomas G. Furin at the cutting edge: From protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol 2002; 3:753–766.
7. Bassi DE, Zhang J, Cenna J. Et al Proprotein convertase inhibition results in decreased skin cell proliferation, tumorigenesis, and metastasis. Neoplasia 2010; 12:516–526.
8. López de Cicco R, Bassi DE, Page R, Klein-Szanto AJP. Furin expression in squamous cell carcinomas of the oral cavity and other sites evaluated by tissue microarray technology. Acta Odontol Latinoam 2002; 15:29–37.
9. Page RE, Klein-Szanto AJP, Litwin S, et al. Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer. Cell Oncol 2007; 29:289–299.
10. Klein-Szanto AJ, Zhang J, Bassi DE. Proprotein Convertases in gynecological cancers. Colloquium Series on Protein Activation and Cancer 2012; 1:1–43, San Rafael (CA): Morgan & Claypool Life Sciences 2012.
11. D'Anjou F, Routhier S, Perreault JP, et al. Molecular validation of PACE4 as a target in prostate cancer. Transl Oncol 2011; 4:157–172.
12. Scamuffa N, Siegfried G, Bontemps Y, et al. Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest 2008; 118:352–363.
13. Pei D, Weiss SH. Furin-dependent intracellular activation of the human stromelysin-3 zymogen. Nature 1995; 375:244–247.
14. Leitlein J, Aulwurm S, Waltereit R, et al. Processing of immunosuppressive pro-TGF-β1,2 by human glioblastoma cells involves cytoplasmic and secreted furin-like proteases. J Immunol 2001; 166:7238–7243.
15. Dubois CM, Blanchette F, Laprise MH, et al. Evidence that furin is an authentic transforming growth factor-beta1- converting enzyme. Am J Pathol 2001; 158:305–316.
16. Khatib AM, Siegfried G, Prat A, et al. Inhibition of proprotein convertases is associated with loss of growth and tumorigenicity of HT-29 human colon carcinoma cells: Importance of insulin-like growth factor-1 (IGF-1) receptor processing in IGF-1-mediated functions. J Biol Chem 2001; 276:30686–30693.
17. Siegfried G, Basak A, Cromlish JA, et al. The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis. J Clin Invest 2003; 111:1723–1732.
18. Basak A, Khatib A-M, Mohottalage, et al. A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C. PLoS ONE 2009; 4:e7700.
19. Schalken JA, Roebroek AJ, Oomen, et al. Fur gene expression as a discriminating marker for small cell and nonsmall cell lung carcinomas. J Clin Invest 1987; 80:1545–1549.
20. Mbikay M, Sirois F, Yao J, et al. Comparative analysis of expression of the proprotein convertases furin, PACE4, PC1 and PC2 in human lung tumours. Br J Cancer 1997; 75:1509–1514.
21. Demidyuk I, Shubin AV, Gasanov EV, et al. Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios. PLoS ONE 2013; 8:e55752.
22. López de Cicco R, Bassi D, Benavides F, et al. Inhibition of proprotein convertases: Approaches to block squamous carcinoma development and progression. Mol Carcinog 2007; 46:654–659.
23. Lalou C, Scamuffa N, Mourah S, et al. Inhibition of the proprotein convertases represses the invasiveness of human primary melanoma cells with altered p53, CDKN2A and N-Ras genes. PLoS ONE 2010; 5:e9992.
24. Ramos Molina B, Lick AN, Blanco EH, et al. Identification of potent and compartment-selective small molecule furin inhibitors using cell-based assays. Biochem Pharmacol 2015; 96:107–118.
25. Couture F, Kwiatkowska A, Dory YL, et al. Therapeutic uses of furin and its inhibitors: A patent review. Expert Opin Ther Pat 2015; 25:379–396.
26. Hardes K, Becker GL, Lu Y, et al. Novel Furin inhibitors with potent anti-infectious activity. Chem Med Chem 2015; 10:1218–1231.
27. Senzer N, Barve M, Kuhn J, et al. Phase I trial of “bi-shRNAi(furin)/GMCSF DNA/autologous tumor cell“ vaccine (FANG) in advanced cancer. Mol Ther 2012; 20:679–686.
28. Nemunaitis J, Barve M, Orr D, et al. Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver. Oncology 2014; 87:21–29.
29. Ghisoli M, Barve M, Schneider R, et al. Pilot trial of FANG immunotherapy in ewing's sarcoma. Mol Ther 2015; 23:1103–1109.
30. Constam DB. Regulation of TGFβ and related signals by precursor processing. Sem Cell Develop Biol 2014; 32:85–97.
31. Ming MO, Wan YY, Sanjabi S, et al. Transforming growth factor beta regulation of immune responses. Annual Rev Immunol 2006; 24:99–146.
32. Bassi DE, Lopez De Cicco R, Mahloogi H, et al. Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells. Proc Natl Acad Sci USA 2001; 98:10326–10331.
33. Mercapide J, Lopez R, Bassi DE, et al. Alpha-1 PDX inhibits astocytoma growth and invasiveness. Clin Cancer Res 2002; 8:1740–1746.
34. Siegfried G, Basak A, Prichett-Pejic W, et al. Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases. Oncogene 2005; 24:6925–6935.