Cooperation between STAT3 and c-Jun Suppresses Fas Transcription

• Published in: Molecular cell Vol. 7; no. 3; pp. 517 - 528
• Main Authors: Ivanov, Vladimir N, Bhoumik, Anindita, Krasilnikov, Mikhail, Raz, Regina, Owen-Schaub, Laurie B, Levy, David, Horvath, Curt M, Ronai, Ze'ev
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2001
• Subjects: Animals; Apoptosis - radiation effects; c-Jun protein; DNA - genetics; DNA - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fas Ligand Protein; fas Receptor - biosynthesis; fas Receptor - genetics; fas Receptor - metabolism; FasL protein; Fibroblasts; Gene Expression Regulation; Humans; Melanoma - genetics; Melanoma - pathology; Melanoma - radiotherapy; Membrane Glycoproteins - metabolism; Mice; Promoter Regions, Genetic - genetics; Protein Binding - radiation effects; Proto-Oncogene Proteins c-jun - antagonists & inhibitors; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Radiation Tolerance - genetics; Radiation Tolerance - radiation effects; Response Elements - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sequence Deletion - genetics; STAT3 Transcription Factor; Trans-Activators - antagonists & inhibitors; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factor AP-1 - metabolism; Transcription, Genetic - genetics; Transcriptional Activation - genetics; Tumor Cells, Cultured; Ultraviolet Rays; Up-Regulation - genetics
• ISSN: 1097-2765; 1097-4164
• DOI: 10.1016/S1097-2765(01)00199-X

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.