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

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

Research output: Contribution to journalArticle

65 Citations (Scopus)

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

Fingerprint

CASP8 and FADD-Like Apoptosis Regulating Protein
Prostatic Neoplasms
Apoptosis
Neoplasms
Cell Death
Tumor Necrosis Factor-alpha
Ligands
Messenger RNA
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Zhang, X., Zhang, L., Yang, H., Huang, X., Otu, H. H., Libermann, T. A., ... Olumi, A. F. (2007). c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells. Cancer Research, 67(19), 9425-9434. https://doi.org/10.1158/0008-5472.CAN-07-1310

c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells. / Zhang, Xiaoping; Zhang, Liang; Yang, Hongmei; Huang, Xu; Otu, Hasan H; Libermann, Towia A.; DeWolf, William C.; Khosravi-Far, Roya; Olumi, Aria F.

In: Cancer Research, Vol. 67, No. 19, 01.10.2007, p. 9425-9434.

Research output: Contribution to journalArticle

Zhang, X, Zhang, L, Yang, H, Huang, X, Otu, HH, Libermann, TA, DeWolf, WC, Khosravi-Far, R & Olumi, AF 2007, 'c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells', Cancer Research, vol. 67, no. 19, pp. 9425-9434. https://doi.org/10.1158/0008-5472.CAN-07-1310
Zhang, Xiaoping ; Zhang, Liang ; Yang, Hongmei ; Huang, Xu ; Otu, Hasan H ; Libermann, Towia A. ; DeWolf, William C. ; Khosravi-Far, Roya ; Olumi, Aria F. / c-Fos as a proapoptotic agent in TRAIL-induced apoptosis in prostate cancer cells. In: Cancer Research. 2007 ; Vol. 67, No. 19. pp. 9425-9434.
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