Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells

Wu Guo Deng, Masahiko Nishizaki, Bingliang Fang, Jack A. Roth, Lin Ji

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

FHIT is a novel tumor suppressor gene located at human chromosome 3p14.2. Restoration of wild-type FHIT in 3p14.2-deficient human lung cancer cells inhibits cell growth and induces apoptosis. In this study, we analyzed potential upstream/downstream molecular targets of the FHIT protein and found that FHIT specifically targeted and regulated death receptor (DR) genes in human non-small-cell lung cancer (NSCLC) cells. Exogenous expression of FHIT by a recombinant adenoviral vector (Ad)-mediated gene transfer upregulated expression of DR genes. Treatment with a recombinant TRAIL protein, a DR-specific ligand, in Ad-FHIT-transduced NSCLC cells considerably enhanced FHIT-induced apoptosis, further demonstrating the involvement of DRs in FHIT-induced apoptosis. Moreover, we also found that FHIT targeted downstream of the DR-mediated signaling pathway. FHIT overexpression disrupted mitochondrial membrane integrity and activated multiple pro-apoptotic proteins in NSCLC cell. These results suggest that FHIT induces apoptosis through a sequential activation of DR-mediated pro-apoptotic signaling pathways in human NSCLC cells.

Original languageEnglish
Pages (from-to)993-999
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume355
Issue number4
DOIs
Publication statusPublished - Apr 20 2007
Externally publishedYes

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Keywords

  • Apoptosis
  • Caspase
  • Death receptor
  • FHIT
  • Lung cancer
  • Tumor suppressor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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