The roles of ATF2 (activating transcription factor 2) in tumorigenesis

Gozdecka, Malgorzata; Breitwieser, Wolfgang

doi:10.1042/bst20110630

Cited by 67 publications

(58 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor-promoting role of ATF2 has been implicated in several types of cancer, such as melanoma and skin carcinoma [32]. Here, our data suggested for the first time the involvement of ATF2 in EHCC, as phosphorylation of ATF2 was increased in EHCC samples.…”

Section: Discussionsupporting

confidence: 56%

WWOX Suppresses Cell Growth and Induces Cell Apoptosis via Inhibition of P38 Nuclear Translocation in Cholangiocarcinoma

Wang

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Extrahepatic cholangiocarcinoma (EHCC) is the second most common primary hepatic malignancy, and is associated with high morbidity and mortality. We previously reported the decreased expression of WWOX in EHCC samples, but the underlying mechanism remained unclear. Methods: Immunoprecipitation and immunofluorescence were performed to examine the interaction of WWOX and P38 MAPK. Western blot was carried out to detect the expression of ATF2 and eIF-4E. MTT, colony formation, and Annexin V-FITC assays were performed to detect the cell proliferation and apoptosis. IHC was performed to detect the protein expression in clinical samples. Results: WWOX interacted with P38 and modulated its sub-cellular localization, leading to the cytoplasmic retention of P38. WWOX over-expression inhibited the phosphorylation of ATF2 and eIF-4E, while exogenous P38 reversed this reduction in phosphorylation. Ectopic expression of WWOX in EHCC cells led to inhibited proliferation and stimulated apoptosis in a P38 MAPK-dependent manner. In addition, we found a negative association of WWOX with nuclear localization of P38 and expression of phosphorylated ATF2 in EHCC samples. Conclusion: Our data demonstrated the role of WWOX in EHCC progression, revealing the potential of WWOX/p-ATF2 as a novel diagnostic and prognostic marker, and therapeutic target for EHCC.

show abstract

Section: Discussionsupporting

confidence: 56%

WWOX Suppresses Cell Growth and Induces Cell Apoptosis via Inhibition of P38 Nuclear Translocation in Cholangiocarcinoma

Wang

et al. 2014

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…ATF-2 is phosphorylated as a result of the activation of JNK/ SAPK or p38 MPAK, thereby promoting AP-1-dependent transcription of apoptotic genes, including Bcl-2 (19,39). ATF-2 is known to regulate target genes by histone modification (20). It is also known that core histone methyltransferase methylation can lead to gene silencing.…”

Section: Discussionmentioning

confidence: 99%

“…Cambogin decreased Bcl-2 expression by ATF-2-mediated epigenetic regulation ATF-2, a component of AP-1 transcription factor, can be activated upon the stimulation of JNK/SAPK, which led to an increase in cell apoptosis in several types of cancers (19,20). Therefore, we sought to find out whether cambogin induces the phosphorylation of ATF-2 of MCF-7 cells.…”

Section: Screening For Differentially Expressed Proteins and Protein mentioning

confidence: 99%

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Shen

Xie

Wang

et al. 2015

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Cambogin is a polycyclic polyprenylated acylphoroglucinol (PPAP) from the Garcinia genus, which has been used traditionally for cancer treatment across Southeastern Asia. In this study, we found that cambogin inhibited breast cancer cell proliferation and induced cell apoptosis in vitro. Cambogin induced the activation of the caspase-independent mitochondrial apoptotic pathway, as indicated by an increase in the ratio of Bax/Bcl-2 and the nuclear translocation of apoptosis inducing factor (AIF). Two-dimensional gel electrophoresis and mass spectrometry revealed that the expression of proteins involving in the radical oxygen species (ROS) pathway was among the most affected upon cambogin treatment. Cambogin enhanced cellular ROS production, and induced the activation of the ASK1-MKK4/MKK7-JNK/SAPK signaling pathway. Pretreatment with ROS scavenger N-acetylcysteine (NAC), an antioxidant, or the JNK inhibitor SP600125 was able to restore cell viability in the presence of cambogin. Importantly, cambogin treatment led to the activation of activating transcription factor-2 (ATF-2) and the trimethylation of histone H3K9 in the activator protein 1 (AP-1) binding region of the Bcl-2 gene promoter. Finally, cambogin exhibited a potential antitumor effect in MCF-7 breast cancer xenografts without apparent toxicity. Taken in conjunction, the present study indicates that cambogin can induce breast adenocarcinoma cell apoptosis and therefore represents therapeutic potential for cancer treatment.

show abstract

“…8 Either p38 or ATF2 play dual roles in different tumors, and we speculated that the differences between our results and the previous one may attribute to a number of factors, including different type of transfected cells, condition of transfection, different type of plasmid, degree of ectopically introduced gene, and other reasons. 15,16 Figure 4. Noxin activated P38 signaling pathway.…”

Section: Discussionmentioning

confidence: 99%

Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway

Zhang

Fan

et al. 2017

Tumour Biol.

View full text Add to dashboard Cite

Noxin (also called chromosome 11 open reading frame 82 or DNA damage-induced apoptosis suppressor) is associated with anti-apoptosis and cell proliferation in response to stress signals. However, to our knowledge, the role of Noxin in regulating cell proliferation is still controversial and there are no reports of the function and clinicopathological association in breast cancer. In this study, immunohistochemistry results showed that Noxin expression was significantly correlated with advanced tumor-node-metastasis stage (p = 0.027), positive regional lymph node metastasis (p = 0.002), and poor overall survival (p = 0.002). Proliferation assay results showed that Noxin obviously promoted the ability of proliferation of normal breast cells. Subsequent western blot results revealed that Cyclin D1 and Cyclin E1 were upregulated by overexpressing Noxin, whereas Cyclin D1 and Cyclin E1 were downregulated after depleting Noxin. The levels of phosphorylated P38 and activating transcription factor 2 were obviously increased after overexpressing Noxin, and their expression was downregulated accordingly by transfecting Noxin-small interfering RNA. Moreover, P38 inhibitor counteracted the elevating expression of phosphorylated activating transcription factor 2, Cyclin D1, and Cyclin E1 induced by Noxin overexpression and thereby reversed the effect of Noxin overexpression on facilitating cell growth. Taken together, our studies indicated that Noxin was overexpressed in breast cancer and its positive expression was significantly correlated with advance tumor-node-metastasis stage, positive lymph node metastasis, and poor prognosis. Noxin facilitated the expression of Cyclin D1 and Cyclin E1 through activating P38-activating transcription factor 2 signaling pathway, thus enhanced cell growth of breast cancer.

show abstract

The roles of ATF2 (activating transcription factor 2) in tumorigenesis

Cited by 67 publications

References 50 publications

WWOX Suppresses Cell Growth and Induces Cell Apoptosis via Inhibition of P38 Nuclear Translocation in Cholangiocarcinoma

WWOX Suppresses Cell Growth and Induces Cell Apoptosis via Inhibition of P38 Nuclear Translocation in Cholangiocarcinoma

Cambogin Induces Caspase-Independent Apoptosis through the ROS/JNK Pathway and Epigenetic Regulation in Breast Cancer Cells

Noxin promotes proliferation of breast cancer cells via P38-ATF2 signaling pathway

Contact Info

Product

Resources

About