Targeting Proprotein Convertases in Furin-rich Lung Cancer Cells Results in Decreased in Vitro and in Vivo Growth

Overview

Journal Mol Carcinog

Specialties Molecular Biology
Oncology

Date 2016 Sep 2

PMID 27584082

Citations 26

Authors

Daniel E Bassi

Jirong Zhang

Catherine Renner

Andres J Klein-Szanto

Affiliations

Soon will be listed here.

Abstract

Proprotein convertases (PCs) are serine proteases with an active role in the post-translational processing of numerous inactive proteins to active proteins including many substrates of paramount importance in cancer development and progression. Furin (PCSKC3), a well-studied member of this family, is overexpressed in numerous human and experimental malignancies. In the present communication, we treated two furin-overexpressing non-small cell carcinoma (NSCLC) cell lines (Calu-6 and HOP-62) with the PC inhibitor CMK (Decanoyl-Arg-Val-Lys-Arg-chloromethylketone). This resulted in a diminished IGF-1R processing and a simultaneous decrease in cell proliferation of two NSCLC lines. Similarly, growth of subcutaneous xenografts of both cell lines, were partially inhibited by an in vivo treatment with the same drug. These observations point to a potential role of PC inhibitors in cancer therapy. © 2016 Wiley Periodicals, Inc.

Citing Articles

Development and Prospects of Furin Inhibitors for Therapeutic Applications.

Ivachtchenko A, Khvat A, Shkil D Int J Mol Sci. 2024; 25(17).

PMID: 39273149 PMC: 11394684. DOI: 10.3390/ijms25179199.

Plasma cell signatures predict prognosis and treatment efficacy for lung adenocarcinoma.

Shu L, Tang J, Liu S, Tao Y Cell Oncol (Dordr). 2023; 47(2):555-571.

PMID: 37814076 DOI: 10.1007/s13402-023-00883-w.

Inactivation of Attenuated Pancreatic Tumorigenesis in Mice.

Saeki K, Qiu W, Friedman R, Pan S, Lu J, Ichimiya S Cancer Res Commun. 2023; 2(12):1601-1616.

PMID: 36970723 PMC: 10035463. DOI: 10.1158/2767-9764.CRC-22-0106.

Overexpression of the pro-protein convertase furin predicts prognosis and promotes papillary thyroid carcinoma progression and metastasis through RAF/MEK signaling.

Poyil P, Siraj A, Padmaja D, Parvathareddy S, Diaz R, Thangavel S Mol Oncol. 2023; 17(7):1324-1342.

PMID: 36799665 PMC: 10323895. DOI: 10.1002/1878-0261.13396.

Antigen-Specific T Cells and SARS-CoV-2 Infection: Current Approaches and Future Possibilities.

Nova Z, Zemanek T, Botek N Int J Mol Sci. 2022; 23(23).

PMID: 36499448 PMC: 9737069. DOI: 10.3390/ijms232315122.

References

DAnjou F, Routhier S, Perreault J, Latil A, Bonnel D, Fournier I . Molecular Validation of PACE4 as a Target in Prostate Cancer. Transl Oncol. 2011; 4(3):157-72. PMC: 3104696. DOI: 10.1593/tlo.10295. View

Li M, Wan Y, Sanjabi S, Robertson A, Flavell R . Transforming growth factor-beta regulation of immune responses. Annu Rev Immunol. 2006; 24:99-146. DOI: 10.1146/annurev.immunol.24.021605.090737. View

Leitlein J, Aulwurm S, Waltereit R, Naumann U, Wagenknecht B, Garten W . Processing of immunosuppressive pro-TGF-beta 1,2 by human glioblastoma cells involves cytoplasmic and secreted furin-like proteases. J Immunol. 2001; 166(12):7238-43. DOI: 10.4049/jimmunol.166.12.7238. View

Dubois C, Blanchette F, Laprise M, Leduc R, Grondin F, Seidah N . Evidence that furin is an authentic transforming growth factor-beta1-converting enzyme. Am J Pathol. 2001; 158(1):305-16. PMC: 1850265. DOI: 10.1016/s0002-9440(10)63970-3. View

Demidyuk I, Shubin A, Gasanov E, Kurinov A, Demkin V, Vinogradova T . Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios. PLoS One. 2013; 8(2):e55752. PMC: 3567108. DOI: 10.1371/journal.pone.0055752. View

Khatib A, Siegfried G, Prat A, Luis J, Chretien M, Metrakos P . 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(33):30686-93. DOI: 10.1074/jbc.M101725200. View

Siegfried G, Basak A, Cromlish J, Benjannet S, Marcinkiewicz J, Chretien M . The secretory proprotein convertases furin, PC5, and PC7 activate VEGF-C to induce tumorigenesis. J Clin Invest. 2003; 111(11):1723-32. PMC: 156106. DOI: 10.1172/JCI17220. View

Taylor N, Van de Ven W, Creemers J . Curbing activation: proprotein convertases in homeostasis and pathology. FASEB J. 2003; 17(10):1215-27. DOI: 10.1096/fj.02-0831rev. View

Nemunaitis J, Barve M, Orr D, Kuhn J, Magee M, Lamont J . Summary of bi-shRNA/GM-CSF augmented autologous tumor cell immunotherapy (FANG™) in advanced cancer of the liver. Oncology. 2014; 87(1):21-9. DOI: 10.1159/000360993. View

10.

Scamuffa N, Siegfried G, Bontemps Y, Ma L, Basak A, Cherel G . Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest. 2007; 118(1):352-63. PMC: 2117762. DOI: 10.1172/JCI32040. View

11.

Thomas G . Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002; 3(10):753-66. PMC: 1964754. DOI: 10.1038/nrm934. View

12.

Bassi D, Zhang J, Cenna J, Litwin S, Cukierman E, Klein-Szanto A . Proprotein convertase inhibition results in decreased skin cell proliferation, tumorigenesis, and metastasis. Neoplasia. 2010; 12(7):516-26. PMC: 2907578. DOI: 10.1593/neo.92030. View

13.

Scamuffa N, Calvo F, Chretien M, Seidah N, Khatib A . Proprotein convertases: lessons from knockouts. FASEB J. 2006; 20(12):1954-63. DOI: 10.1096/fj.05-5491rev. View

14.

Bassi D, Lopez de Cicco R, Mahloogi H, Zucker S, Thomas G, Klein-Szanto A . Furin inhibition results in absent or decreased invasiveness and tumorigenicity of human cancer cells. Proc Natl Acad Sci U S A. 2001; 98(18):10326-31. PMC: 56960. DOI: 10.1073/pnas.191199198. View

15.

De Cicco R, Bassi D, Benavides F, Conti C, Klein-Szanto A . Inhibition of proprotein convertases: approaches to block squamous carcinoma development and progression. Mol Carcinog. 2007; 46(8):654-9. DOI: 10.1002/mc.20331. View

16.

Siegfried G, Basak A, Prichett-Pejic W, Scamuffa N, Ma L, Benjannet S . Regulation of the stepwise proteolytic cleavage and secretion of PDGF-B by the proprotein convertases. Oncogene. 2005; 24(46):6925-35. DOI: 10.1038/sj.onc.1208838. View

17.

Page R, Klein-Szanto A, Litwin S, Nicolas E, Al-Jumaily R, Alexander P . Increased expression of the pro-protein convertase furin predicts decreased survival in ovarian cancer. Cell Oncol. 2007; 29(4):289-99. PMC: 4617813. DOI: 10.1155/2007/930321. View

18.

Lalou C, Scamuffa N, Mourah S, Plassa F, Podgorniak M, Soufir N . 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(4):e9992. PMC: 2852400. DOI: 10.1371/journal.pone.0009992. View

19.

Basak A, Khatib A, Mohottalage D, Basak S, Kolajova M, Bag S . A novel enediynyl peptide inhibitor of furin that blocks processing of proPDGF-A, B and proVEGF-C. PLoS One. 2009; 4(11):e7700. PMC: 2778948. DOI: 10.1371/journal.pone.0007700. View

20.

Yana I, Weiss S . Regulation of membrane type-1 matrix metalloproteinase activation by proprotein convertases. Mol Biol Cell. 2000; 11(7):2387-401. PMC: 14927. DOI: 10.1091/mbc.11.7.2387. View