Title: Liver-Specific Inactivation of the Proprotein Convertase FURIN Leads to Increased Hepatocellular Carcinoma Growth
Authors: Declercq, Jeroen
Brouwers, Bas
Pruniau, Vincent
Stijnen, Pieter
Tuand, Krizia
Meulemans, Sandra
Prat, Annik
Seidah, Nabil G
Khatib, Abdel-Majid
Creemers, John # ×
Issue Date: 2015
Publisher: Hindawi Publishing Corporation
Series Title: BioMed Research International vol:2015 pages:148651
Article number: 10.1155/2015/148651
Abstract: Proprotein convertases are subtilisin-like serine endoproteases that cleave and hence activate a variety of proproteins, including growth factors, receptors, metalloproteases, and extracellular matrix proteins. Therefore, it has been suggested that inhibition of the ubiquitously expressed proprotein convertase FURIN might be a good therapeutic strategy for several tumor types. Whether this is also the case for hepatocellular carcinoma (HCC) is currently not clear. In a mouse model for HCC expression of Furin was not altered in the tumors, while those of PC7, PC5/6, and PACE4 significantly decreased, at least at some time points. To investigate the impact of Furin inhibition on the development and progression of HCC in this model, Furin was genetically ablated in the liver. Furin inactivation resulted in an increased tumor mass after 5 weeks. This was not caused by decreased apoptosis, since no differences in the apoptosis index could be observed. However, it could at least partially be explained by increased hepatocyte proliferation at 5 weeks. The tumors of the Furin knockout mice were histologically similar to those in wild type mice. In conclusion, liver-specific Furin inhibition in HCC enhances the tumor formation and will not be a good therapeutic strategy for this tumor type.
ISSN: 2314-6133
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Laboratory for Biochemical Neuroendocrinology
× corresponding author
# (joint) last author

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