CYLD inhibits melanoma growth and progression through suppression of the JNK/AP-1 and β1-integrin signaling pathways

@article{Ke2013CYLDIM,
  title={CYLD inhibits melanoma growth and progression through suppression of the JNK/AP-1 and $\beta$1-integrin signaling pathways},
  author={Hengning Ke and Christina K. Augustine and Vineela D. Gandham and Jane Y. Jin and Douglas S Tyler and Steven K. Akiyama and Russell P. Hall and Jennifer Y. Zhang},
  journal={The Journal of investigative dermatology},
  year={2013},
  volume={133},
  pages={221 - 229}
}
The molecular mechanisms mediating CYLD tumor suppressor function appear to be manifold. Here, we demonstrated that, in contrast to the increased levels of pJNK, CYLD was decreased in a majority of melanoma cell lines and tissues examined. Exogenous expression of CYLD but not its catalytically deficient mutant markedly inhibited melanoma cell proliferation and migration in vitro and subcutaneous tumor growth in vivo. In addition, the melanoma cells expressing exogenous CYLD were unable to form… 
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References

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CYLD Inhibits Tumorigenesis and Metastasis by Blocking JNK/AP1 Signaling at Multiple Levels
CYLD has been recognized as a tumor suppressor due to its dominant genetic linkage to multiple types of epidermal tumors and a range of other cancers. The molecular mechanisms governing CYLD control
Negative Regulation of JNK Signaling by the Tumor Suppressor CYLD*
TLDR
A critical role is reported for CYLD in negatively regulating the c-Jun NH2-terminal kinase (JNK) and a receptor-dependent role of CYLD is suggested in regulating the IκB kinase pathway.
Down-regulation of CYLD expression by Snail promotes tumor progression in malignant melanoma
TLDR
The data suggest that Snail1-mediated suppression of CYLD plays a key role in melanoma malignancy, and tumor thickness and progression-free and overall survival inversely correlated with CYLD expression.
JNK supports survival in melanoma cells by controlling cell cycle arrest and apoptosis
TLDR
It is demonstrated that JNK, and in particular the JNK1 isoform, support the growth of melanoma cells, by controlling either cell cycle progression or apoptosis depending on the cellular context.
c-Jun promotes whereas JunB inhibits epidermal neoplasia.
TLDR
It is indicated that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.
The tumor suppressor CYLD regulates entry into mitosis
TLDR
It is shown that CYLD is also required for timely entry into mitosis, and it is proposed that this additional function of CYLD could provide an explanation for the benign nature of most cylindroma lesions.
The BRG1- and hBRM-Associated Factor BAF57 Induces Apoptosis by Stimulating Expression of the Cylindromatosis Tumor Suppressor Gene
TLDR
Findings demonstrate the importance of BAF57 in cell growth regulation and provide a novel link between hSWI/SNF chromatin remodelers and apoptosis.
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TLDR
Functional relevant loss of CYLD expression may contribute to tumor development and progression, and may provide a new target for therapeutic strategies.
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TLDR
JNK2 is activated in more than 70% of human squamous cell carcinoma (SCC) samples and that inhibition of JNK2 pharmacologically or genetically impairs tumorigenesis of human SCC cells is reported, indicating that JNK1 is sufficient to couple with oncogenic Ras to transform primary human epidermal cells into malignancy with features of SCC.
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