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Furin overexpression suppresses tumor growth and predicts a better postoperative disease-free survival in hepatocellular carcinoma.

Abstract
Furin is a member of the pro-protein convertase family. It processes several growth regulatory proteins into their active forms, which are critical to tumor progression, metastasis, and angiogenesis. Furin over-expression could occur in liver cancer and a previous study showed that over-expression of furin promoted HepG2 cell invasion in tail vein xenograft models. However, the clinical relevance of furin expression in hepatocellular carcinoma (HCC) remained unknown. Surprisingly, in a postoperative survival analysis for HCC patients, it was found that the tumor/non-tumor (T/N) ratio of furin expression ≥ 3.5 in HCC tissues predicted a better postoperative disease-free survival (DFS) (P = 0.010; log-rank test). Furthermore, subcutaneous xenograft experiments demonstrated a significant suppression effect of tumor growth in the furin-overexpressed xenografts (Huh7-Furin) compared to the mock control. Administration of a synthetic furin inhibitor for inhibition of the pro-protein convertase activity, decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decRVKR-CMK), to the Huh7-Furin xenograft bearing mice restored the repression effect of tumor growth. In contrast, administration of decRVKR-CMK to the mock Huh7 xenograft bearing mice showed no change in growth rate. In conclusion, furin overexpression inhibited HCC tumor growth in a subcutaneous xenograft model and predicted a better postoperative DFS in clinical analysis.
AuthorsYa-Hui Huang, Kwang-Huei Lin, Chen-Hsin Liao, Ming-Wei Lai, Yi-Hsin Tseng, Chau-Ting Yeh
JournalPloS one (PLoS One) Vol. 7 Issue 7 Pg. e40738 ( 2012) ISSN: 1932-6203 [Electronic] United States
PMID22808247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Amino Acid Chloromethyl Ketones
  • Intercellular Signaling Peptides and Proteins
  • decanoylRVKRchloromethylketone
  • Furin
Topics
  • Amino Acid Chloromethyl Ketones (pharmacology)
  • Animals
  • Apoptosis (drug effects)
  • Carcinoma, Hepatocellular (metabolism, pathology, surgery)
  • Cell Line, Tumor
  • Cell Proliferation (drug effects)
  • Cell Survival (drug effects)
  • Disease-Free Survival
  • Female
  • Furin (antagonists & inhibitors, metabolism)
  • Humans
  • Intercellular Signaling Peptides and Proteins (pharmacology)
  • Liver Neoplasms (metabolism, pathology, surgery)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Postoperative Care
  • Xenograft Model Antitumor Assays

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