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Mol Cell. 2001 Mar;7(3):517-28.

Cooperation between STAT3 and c-jun suppresses Fas transcription.

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1
The Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, New York 10029, USA.

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.

PMID:
11463377
DOI:
10.1016/s1097-2765(01)00199-x
[Indexed for MEDLINE]
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