Cooperation between STAT3 and c-Jun suppresses Fas transcription

Vladimir N. Ivanov, Anindita Bhoumik, Mikhail Krasilnikov, Regina Raz, Laurie B. Owen-Schaub, David Levy, Curt M. Horvath, Ze'ev Ronai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

198 Scopus citations

Abstract

Decreased Fas expression during tumor progression often results in a loss of Fas-ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse correlation between the degree of Fas cell surface expression, tumorigenicity, and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in melanoma cells efficiently increased Fas expression and sensitized cells to FasL-induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas cell surface expression and higher sensitivity to FasL-mediated apoptosis. Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated transcriptional activation. Our findings indicate that Stat3 oncogenic activities could also be mediated through its cooperation with c-Jun, resulting in downregulation of Fas surface expression, which is implicated in the tumor's ability to resist therapy and metastasize.

Original languageEnglish (US)
Pages (from-to)517-528
Number of pages12
JournalMolecular cell
Volume7
Issue number3
DOIs
StatePublished - Mar 1 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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