Electrical & Computer Engineering, Department of

 

ORCID IDs

Hasan H. Otu

Date of this Version

2007

Citation

Cancer Res. 2007 October 1; 67(19): 9425–9434

Comments

doi:10.1158/0008-5472.CAN-07-1310

Abstract

Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)/Apo-2L promotes apoptosis in cancer cells while sparing normal cells. Although many cancers are sensitive to TRAIL-induced apoptosis, some evade the proapoptotic effects of TRAIL. Therefore, differentiating molecular mechanisms that distinguish between TRAIL-sensitive and TRAIL-resistant tumors are essential for effective cancer therapies. Here, we show that c-Fos functions as a proapoptotic agent by repressing the antiapoptotic molecule c-FLIP(L). c-Fos binds the c-FLIP(L) promoter, represses its transcriptional activity, and reduces c-FLIP(L) mRNA and protein levels. Therefore, c-Fos is a key regulator of c-FLIP(L), and activation of c-Fos determines whether a cancer cell will undergo cell death after TRAIL treatment. Strategies to activate c-Fos or inhibit c-FLIP(L) may potentiate TRAILbased proapoptotic therapies.

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