Eferl, R. & Wagner, E.F. AP-1: a double-edged sword in tumorigenesis. Nat. Rev. Cancer 3, 859-868

Research Institute of Molecular Pathology, Dr Bohr Gasse 7, A-1030 Vienna, Austria.
Nature reviews. Cancer (Impact Factor: 37.4). 12/2003; 3(11):859-68. DOI: 10.1038/nrc1209
Source: PubMed


The AP-1 transcription factor is a dimeric complex that contains members of the JUN, FOS, ATF and MAF protein families. AP-1 proteins are primarily considered to be oncogenic, but recent studies have challenged this view — some AP-1 proteins, such as JUNB and c-FOS, have been shown to have tumour-suppressor activity. Here, we focus on the JUN and FOS proteins and aim to offer a new perspective on the molecular mechanisms that regulate the oncogenic and anti-oncogenic effects of AP-1 in tumour development.

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    • "The main AP - 1 proteins in mammalian cells are Fos and Jun ( Eferl and Wagner , 2003 ) . In mammals , there are four Fos proteins ( c - Fos , FosB , Fra1 and Fra2 ) and three Jun proteins ( c - Jun , JunB and JunD ) ( Eferl and Wagner , 2003 ) . In contrast to vertebrates , only one Jun and one Fos protein appear to be present in Drosophila ( Kockel et al . "
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    ABSTRACT: Growing evidence indicates that activator protein-1 (AP-1) plays a major role in stimulating the transcription of immune effector molecules in cellular response to an incredible array of stimuli, including growth factors, cytokines, cellular stresses and bacterial and viral infection. Here, we reported the isolation and characterization of a cDNA from Litopenaeus vannamei encoding the full-length c-Fos protein (named as Lvc-Fos). The predicted amino acid sequences of Lvc-Fos contained a basic-leucine zipper (bZIP) domain, which was characteristic of members of the AP-1 family. Immunoprecipitation and native-PAGE assays determined that Lvc-Fos could interact with the Lvc-Jun, a homolog of c-Jun family in L. vannamei, in a heterodimer manner. Further investigation demonstrated that Lvc-Fos and Lvc-Jun were expressed in all tested tissues and located in the nucleus. Real-time RT-PCR analysis showed both Lvc-Fos and Lvc-Jun in gills were up-regulated during Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenges. In addition, reporter gene assays indicated Lvc-Fos and Lvc-Jun could activate the expression of antimicrobial peptides (AMPs) of Drosophila and shrimp, as well as WSSV immediate early (IE) genes wsv069 and wsv249, in a different manner. Knockdown of Lvc-Fos or Lvc-Jun by RNA interference (RNAi) resulted in higher mortalities of L. vannamei after infection with V. parahaemolyticus, suggesting that Lvc-Fos and Lvc-Jun might play protective roles in bacterial infection. However, silencing of Lvc-Fos or Lvc-Jun in shrimp caused lower mortalities and virus loads under WSSV infection, suggesting that Lvc-Fos and Lvc-Jun could be engaged for WSSV replication and pathogenesis. In conclusion, our results provided experimental evidence and novel insight into the roles of L. vannamei AP-1 in bacterial and viral infection. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Apr 2015 · Developmental and comparative immunology
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    • "Activation of the AP-1 signaling is well documented in promoting the growth, proliferation, invasion and metastasis of human lung cancer cells [63] [64]. On one hand, activation of the AP-1 complex can induce the expression of downstream targeted genes including matrix metalloproteinase MMP1, MMP2, MMP3 and MMP9, osteonectin, autotaxin, etc [65] [66]. "
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    ABSTRACT: Members of the Peroxiredoxin (Prx) family are major cellular antioxidants that scavenge hydrogen peroxide and play essential roles in oxidative stress and cell signaling. 2-Cys Prxs, including Prx1, 2, 3 and 4, have been indicated in multiple oncogenic signaling pathways and thus may contribute to various processes of cancer development. The significance of 2-Cys Prxs in lung cancer development and their biological function in signal transduction have not been fully investigated. In this study we analyzed the expression of 2-Cys Prxs in lung cancer, and examined their levels of expression in a variety of cell lines established from human lung normal or cancer tissues. We found that 2-Cys Prxs, in particular, Prx1 and Prx4, were preferentially expressed in cell lines derived from human lung cancer. Through isoform specific knockdown of individual Prx, we demonstrated that Prx1 and Prx4 (but not Prx3) were required for human lung cancer A549 cells to form soft agar colony and to invade through matrigel in culture. Knockdown of Prx1 or Prx4 significantly reduced the activation of c-Jun and repressed the AP-1 mediated promoter activity. In mouse xenograft models, knockdown of Prx4 in A549 cells reduced subcutaneous tumor growth and blocked metastasis formation initiated through tail vein injection. Moreover, overexpression of Prx1 or Prx4 further enhanced the malignancy of A549 cells both in culture and in mouse xenografts in vivo. These data provide an in-depth understanding of the contribution of Prx1 and Prx4 to lung cancer development and are of importance for future development of therapeutic methods that targeting 2-Cys Prxs.
    Full-text · Article · Sep 2014 · American Journal of Cancer Research
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    • "pathway (Eferl and Wagner 2003). Activated AP-1 performs a prominent role in controlling the expression of MMP-9 gene (Crowe and Brown 1999). "
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    ABSTRACT: Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.
    Full-text · Article · Sep 2014 · Biochemistry and Cell Biology
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