Possible Involvement of Cyclophilin A Processing in Fumagillin-Induced Suppression of Cholangiocarcinoma Cell Proliferation

Kanlayanee Sawanyawisuth, Chaisiri Wongkham, Gregory J. Riggins, Sopit Wongkham, Norie Araki

Research output: Contribution to journalArticle

Abstract

Methionine aminopeptidase 2 (MetAP2), a proteolytic enzyme that removes the N-terminal methionine from newly synthesized cellular proteins, plays roles in the development of various cancers and has been found to be over-expressed in cholangiocarcinoma (CCA). Fumagillin, a specific MetAP2 inhibitor, suppresses CCA cell proliferation. In order to determine the molecular mechanisms involved in the suppression of CCA cell proliferation caused by fumagillin, proteomic analysis was performed on fumagillin-treated CCA cells. Proteins affected by fumagillin were analyzed using 2D gel electrophoresis and matrix-assisted laser desorption ionization time of flight tandem mass spectrometry (MALDI-TOF/TOF). The results showed that the processed form of cyclophilin A (CypA) was greatly decreased in parallel with the suppression of CCA cell proliferation. These results suggest that CypA is possibly a protein substrate of MetAP2 cleavage. Removal of N-terminal methionine by MetAP2 may be essential for proper function of CypA in CCA cell proliferation. MetAP2 and CypA may thus serve as potential therapeutic targets for CCA treatment.

Original languageEnglish (US)
Pages (from-to)137-141
Number of pages5
JournalAsian Pacific Journal of Cancer Prevention
Volume13
Issue numberSUPPL.1
DOIs
StatePublished - 2012

Keywords

  • Bile duct cancer
  • Cholangiocarcinoma
  • Cyclophilin A
  • Fumagillin
  • Methionine aminopeptidase 2

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Public Health, Environmental and Occupational Health
  • Cancer Research

Fingerprint Dive into the research topics of 'Possible Involvement of Cyclophilin A Processing in Fumagillin-Induced Suppression of Cholangiocarcinoma Cell Proliferation'. Together they form a unique fingerprint.

  • Cite this