Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget’s disease

Chen, Si Yuan; Takeuchi, Satoshi; Moroi, Yoichi; Hayashida, Shinsaku; Kido, M.; Tomoeda, Hiroto; Uenotsuchi, Takeshi; Tu, Yuexing; Furue, Masutaka; Urabe, Kazunori

doi:10.1111/j.1600-0560.2008.01076.x

Cited by 13 publications

(13 citation statements)

References 33 publications

(55 reference statements)

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“…For example, increased expression and phosphorylation of ATF2 correlates with increased tumour invasiveness in patients with extramammary Paget's disease143. Furthermore, in vitro studies with MCF10A cells demonstrate that ATF2 signalling driven by p38 mediates the transcription of MMP2, thereby influencing invasive migration78.…”

Section: Ap1 In Tumorigenesismentioning

confidence: 99%

Emerging roles of ATF2 and the dynamic AP1 network in cancer

López-Bergami¹,

Lau²,

Ronai³

2010

Nat Rev Cancer

273

269

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Cooperation among transcription factors is central for their ability to execute specific transcriptional programmes. The AP1 complex exemplifies a network of transcription factors that function in unison under normal circumstances and during the course of tumour development and progression. This Perspective summarizes our current understanding of the changes in members of the AP1 complex and the role of ATF2 as part of this complex in tumorigenesis.Activator protein 1 (AP1) 1,2 functions in almost all areas of eukaryotic cellular behaviour, from cell cycle proliferation and development to stress response and apoptosis. Indeed, AP1 is activated in response to a plethora of extracellular signals from cytokines and growth factors to stress and inflammation 3,4 . The expansive transcriptional repertoire executed by AP1 complexes is propagated from the diverse compositional array of homodimeric or heterodimeric combinations formed by members of the Jun, Atf, Fos and Maf transcription factor families (BOX 1). The dimeric combinations and transcriptional activity observed in vivo are largely influenced by the tissue-specific expression patterns of the individual proteins, and importantly by their specific activating mechanisms and post-translational modifications that facilitate their individual ability to dimerize with other basic leucine zipper (bZIP) domain proteins. This inherently diverse composition of AP1 complexes and their central role in transcriptional regulation places AP1 complexes at a functional epicenter for pathological signal relay in disease, particularly in the context of malignant cellular transformation in which AP1 proteins are often deregulated by oncoprotein signalling [4][5][6] . This Perspective describes the function and cooperation of Jun, Fos and Atf family members in tumour cells, and the emerging function of ATF2 as part of the dynamic AP1 complex. Competing interests statement:The authors declare no competing financial interests. The Ap1 transcription factor complexThe mammalian AP1 proteins are homodimers and heterodimers composed of proteins from the Jun (JUN, JUNB and JUND) and Fos (FOS, FOSB, FRA1 and FRA2) families, and the closely related activating transcription factor (Atf and Creb) subfamily and the Maf subfamily 5 . AP1 constituent proteins are structurally distinguished by a basic leucine zipper (bZIP) domain that is composed of leucine zipper and basic domains. It is through these domains that AP1 proteins dimerize and bind to DNA. These proteins are typically activated through phosphorylation by the indicated upstream kinases. The different AP1 dimers bind to DNA with varying affinities and differ in their transactivation efficiencies 8,15 . Jun proteins can form stable dimers that bind to the AP1 DNA recognition element 5′-TGAC/ GTCA-3′ (also known as TPA response element (TRE)) based on their ability to mediate transcriptional induction in response to the phorbol ester tumour promoter TPA 2,15 . Atf proteins, conversely, form dimers that preferentially bind to c...

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Section: Ap1 In Tumorigenesismentioning

confidence: 99%

Emerging roles of ATF2 and the dynamic AP1 network in cancer

López-Bergami¹,

Lau²,

Ronai³

2010

Nat Rev Cancer

273

269

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“…For example, ATF2 has been reported to promote the development and progression of synovial sarcomas by aberrantly binding to the oncogenic fusion protein SS18-SSX, an interaction that alters its transcriptional activity (63, 64). Altered ATF2 expression and localization have also been implicated in the pathology, progression, and chemoresistance of extramammary Paget’s disease, as well as in prostate and head and neck squamous cancers (65–68). Interestingly, loss of ATF2 has been shown to promote the development of mammary tumors in mouse models, likely via transcriptional deregulation of the cell cycle-related tumor genes Maspin and GADD45 (50, 69).…”

Section: Atf2 In Diseasementioning

confidence: 99%

ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease

Watson

Ronai

Lau

2017

Pharmacological Research

111

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Summary Stringent transcriptional regulation is crucial for normal cellular biology and organismal development. Perturbations in the proper regulation of transcription factors can result in numerous pathologies, including cancer. Thus, understanding how transcription factors are regulated and how they are dysregulated in disease states is key to the therapeutic targeting of these factors and/or the pathways that they regulate. Activating transcription factor 2 (ATF2) has been studied in a number of developmental and pathological conditions. Recent findings have shed light on the transcriptional, post-transcriptional, and post-translational regulatory mechanisms that influence ATF2 function, and thus, the transcriptional programs coordinated by ATF2. Given our current knowledge of its multiple levels of regulation and function, ATF2 represents a paradigm for the mechanistic complexity that can regulate transcription factor function. Thus, increasing our understanding of the regulation and function of ATF2 will provide insights into fundamental regulatory mechanisms that influence how cells integrate extracellular and intracellular signals into a genomic response through transcription factors. Characterization of ATF2 dysfunction in the context of pathological conditions, particularly in cancer biology and response to therapy, will be important in understanding how pathways controlled by ATF2 or other transcription factors might be therapeutically exploited. In this review, we provide an overview of the currently known upstream regulators and downstream targets of ATF2.

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“…383 The results may explain why the activation of DC is paradoxically 384 impaired in arsenical cancers, leading to strikingly reduced contact 385 hypersensitivity reaction to DNCB in the skin [ cell migration and invasion [45]. Similar to the contribution of Bowen's disease [47,48], this study is the first to demonstrate that 415 STAT3 expression is increased in arsenic-induced Bowen's disease. 416 This study showed that STAT3-mediated production of VEGF abro- …”

Section: Q4mentioning

confidence: 76%

“…The increase in VEGF was blocked by inhibiting STAT3 with 45 RNA interference or pharmaceutically with JSI-124. While VEGF by itself minimally induced the expres- 46 sion of CD86 and MHC-II in MDDC, arsenic induced-MDDC activation was abolished by VEGF pretreat- 47 ment. We concluded that the STAT3-VEGF axis in keratinocytes inhibits DC migration in the 48 microenvironment of As-BD, indicating that cellular interactions play an important role in regulating 49 the disease course of arsenical cancers.…”

Section: Q4mentioning

confidence: 88%

STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: A plausible regional mechanism of immunosuppression in arsenical cancers

Hong

Lee

Chen

et al. 2015

Chemico-Biological Interactions

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Concordant overexpression of phosphorylated ATF2 and STAT3 in extramammary Paget’s disease

Abstract: P-ATF2 and p-STAT3 are concordantly overexpressed in EMPD and their expressions may possibly be associated with the tumor stage.

Cited by 13 publications

References 33 publications

Emerging roles of ATF2 and the dynamic AP1 network in cancer

Emerging roles of ATF2 and the dynamic AP1 network in cancer

ATF2, a paradigm of the multifaceted regulation of transcription factors in biology and disease

STAT3-dependent VEGF production from keratinocytes abrogates dendritic cell activation and migration by arsenic: A plausible regional mechanism of immunosuppression in arsenical cancers

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