title: Targeting proprotein convertases in furin-rich lung cancer cells results in decreased in vitro and in vivo growth.
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.
authors: Department of Pathology and Histopathology Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.|Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Daniel E
authors: DE
authors: Bassi
authors: Department of Pathology and Histopathology Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.|Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Jirong
authors: J
authors: Zhang
authors: Department of Pathology and Histopathology Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Catherine
authors: C
authors: Renner
authors: Department of Pathology and Histopathology Facility, Fox Chase Cancer Center, Philadelphia, Pennsylvania.|Cancer Biology Program, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors: Andres J
authors: AJ
authors: Klein-Szanto
mesh_terms: D000072283:A549 Cells; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D045683:Furin / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D009368:Neoplasm Transplantation; D043484:Proprotein Convertases / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D043484:Proprotein Convertases; C468731:FURIN protein, human; D045683:Furin
keywords: IGF-1R; PCSKC3; furin; lung cancer; proprotein convertases; tumor development