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Cooperation between STAT3 and c-Jun Suppresses Fas Transcription

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

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.

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Academic Units
Center for Radiological Research
Publisher
Elsevier
Published Here
August 31, 2015