c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells

Xiaoping Zhang, Liang Zhang, Hongmei Yang, Xu Huang, Hasan Otu, Towia A. Libermann, William C. DeWolf, Roya Khosravi-Far, Aria F. Olumi

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

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 TRAIL-based proapoptotic therapies.

Original languageEnglish (US)
Pages (from-to)9425-9434
Number of pages10
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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