Trail induces cell migration and invasion in apoptosis-resistant cholangiocarcinoma cells

Norihisa Ishimura, Hajime Isomoto, Steven F. Bronk, Gregory J. Gores

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for cancer therapy; however, many cholangiocarcinoma cells are resistant to TRAIL-mediated apoptosis. Resistance to apoptosis may unmask TRAIL signaling cascades favoring tumor biology. Thus our aim was to examine whether TRAIL is expressed by human cholangiocarcinomas, and if so, to determine whether it promotes a malignant phenotype. To address this objective, TRAIL expression in human liver specimens was evaluated by immunohistochemistry. The effect of TRAIL on tumor cell migration, invasion, and proliferation was examined in three human cholangiocarcinoma cell lines. TRAIL expression was upregulated by cholangiocytes in preneoplastic disease, primary sclerosing cholangitis, and human cholangiocarcinoma specimens. TRAIL promoted tumor cell migration and invasion but did not induce cell proliferation. TRAIL-mediated cell migration and invasion was NF-κB dependent. These data demonstrate that TRAIL promotes cell migration and invasion via a NF-κB-dependent pathway in human cholangiocarcinoma cell lines, an observation that has a potential negative implication for TRAIL in cancer therapy.

Original languageEnglish (US)
Pages (from-to)G129-G136
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number1
StatePublished - Jan 2006


  • Cholangiocyte
  • Malignant phenotype
  • Nuclear factor-κB
  • Tumor necrosis factor-related apoptosis-inducing ligand

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)


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