C-Fos As a Proapoptotic Agent in TRAIL-induced Apoptosis in Prostate Cancer Cells

Overview

Journal Cancer Res

Specialty Oncology

Date 2007 Oct 3

PMID 17909052

Citations 42

Authors

Xiaoping Zhang

Liang Zhang

Hongmei Yang

Xu Huang

Hasan Otu

Towia A Libermann

William C DeWolf

Roya Khosravi-Far

Aria F Olumi

Affiliations

Soon will be listed here.

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.

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References

Jin Z, El-Deiry W . Overview of cell death signaling pathways. Cancer Biol Ther. 2005; 4(2):139-63. DOI: 10.4161/cbt.4.2.1508. View

Tanos T, Marinissen M, Coluccio Leskow F, Hochbaum D, Martinetto H, Gutkind J . Phosphorylation of c-Fos by members of the p38 MAPK family. Role in the AP-1 response to UV light. J Biol Chem. 2005; 280(19):18842-52. DOI: 10.1074/jbc.M500620200. View

Drosopoulos K, Roberts M, Cermak L, Sasazuki T, Shirasawa S, Andera L . Transformation by oncogenic RAS sensitizes human colon cells to TRAIL-induced apoptosis by up-regulating death receptor 4 and death receptor 5 through a MEK-dependent pathway. J Biol Chem. 2005; 280(24):22856-67. DOI: 10.1074/jbc.M412483200. View

David J, Mehic D, Bakiri L, Schilling A, Mandic V, Priemel M . Essential role of RSK2 in c-Fos-dependent osteosarcoma development. J Clin Invest. 2005; 115(3):664-72. PMC: 548699. DOI: 10.1172/JCI22877. View

Kreuz S, Siegmund D, Scheurich P, Wajant H . NF-kappaB inducers upregulate cFLIP, a cycloheximide-sensitive inhibitor of death receptor signaling. Mol Cell Biol. 2001; 21(12):3964-73. PMC: 87059. DOI: 10.1128/MCB.21.12.3964-3973.2001. View

Okada S, Obata S, Hatano M, Tokuhisa T . Dominant-negative effect of the c-fos family gene products on inducible NO synthase expression in macrophages. Int Immunol. 2003; 15(11):1275-82. DOI: 10.1093/intimm/dxg126. View

Gao S, Lee P, Wang H, Gerald W, Adler M, Zhang L . The androgen receptor directly targets the cellular Fas/FasL-associated death domain protein-like inhibitory protein gene to promote the androgen-independent growth of prostate cancer cells. Mol Endocrinol. 2005; 19(7):1792-802. PMC: 1855294. DOI: 10.1210/me.2004-0445. View

Tillman K, Oberfield J, Shen X, Bubulya A, Shemshedini L . c-Fos dimerization with c-Jun represses c-Jun enhancement of androgen receptor transactivation. Endocrine. 1998; 9(2):193-200. DOI: 10.1385/ENDO:9:2:193. View

Agrawal S, Agrawal A, Doughty B, Gerwitz A, Blenis J, Van Dyke T . Cutting edge: different Toll-like receptor agonists instruct dendritic cells to induce distinct Th responses via differential modulation of extracellular signal-regulated kinase-mitogen-activated protein kinase and c-Fos. J Immunol. 2003; 171(10):4984-9. DOI: 10.4049/jimmunol.171.10.4984. View

10.

Manak J, de Bisschop N, Kris R, Prywes R . Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990; 4(6):955-67. DOI: 10.1101/gad.4.6.955. View

11.

Wiley S, Schooley K, Smolak P, Din W, Huang C, Nicholl J . Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 1995; 3(6):673-82. DOI: 10.1016/1074-7613(95)90057-8. View

12.

Micheau O, Thome M, Schneider P, Holler N, Tschopp J, Nicholson D . The long form of FLIP is an activator of caspase-8 at the Fas death-inducing signaling complex. J Biol Chem. 2002; 277(47):45162-71. DOI: 10.1074/jbc.M206882200. View

13.

Golks A, Brenner D, Fritsch C, Krammer P, Lavrik I . c-FLIPR, a new regulator of death receptor-induced apoptosis. J Biol Chem. 2005; 280(15):14507-13. DOI: 10.1074/jbc.M414425200. View

14.

Kelley S, Ashkenazi A . Targeting death receptors in cancer with Apo2L/TRAIL. Curr Opin Pharmacol. 2004; 4(4):333-9. DOI: 10.1016/j.coph.2004.02.006. View

15.

Evan G, Littlewood T . A matter of life and cell death. Science. 1998; 281(5381):1317-22. DOI: 10.1126/science.281.5381.1317. View

16.

Chang D, Xing Z, Pan Y, Algeciras-Schimnich A, Barnhart B, Yaish-Ohad S . c-FLIP(L) is a dual function regulator for caspase-8 activation and CD95-mediated apoptosis. EMBO J. 2002; 21(14):3704-14. PMC: 125398. DOI: 10.1093/emboj/cdf356. View

17.

Quan T, He T, Voorhees J, Fisher G . Ultraviolet irradiation induces Smad7 via induction of transcription factor AP-1 in human skin fibroblasts. J Biol Chem. 2004; 280(9):8079-85. PMC: 3738262. DOI: 10.1074/jbc.M409647200. View

18.

Acquaviva C, Bossis G, Ferrara P, Brockly F, Jariel-Encontre I, Piechaczyk M . Multiple degradation pathways for Fos family proteins. Ann N Y Acad Sci. 2002; 973:426-34. DOI: 10.1111/j.1749-6632.2002.tb04677.x. View

19.

Herdegen T, Leah J . Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins. Brain Res Brain Res Rev. 1998; 28(3):370-490. DOI: 10.1016/s0165-0173(98)00018-6. View

20.

Ricci M, Jin Z, Dews M, Yu D, Thomas-Tikhonenko A, Dicker D . Direct repression of FLIP expression by c-myc is a major determinant of TRAIL sensitivity. Mol Cell Biol. 2004; 24(19):8541-55. PMC: 516765. DOI: 10.1128/MCB.24.19.8541-8555.2004. View