Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling.

@article{Wu2015EpigeneticSO,
  title={Epigenetic silencing of DUSP9 induces the proliferation of human gastric cancer by activating JNK signaling.},
  author={Fang Wu and Tianmin Lv and Gang Chen and Huajun Ye and Wei Wu and Gang Li and Fa-chao Zhi},
  journal={Oncology reports},
  year={2015},
  volume={34 1},
  pages={
          121-8
        }
}
Dual-specificity phosphatase 9 (DUSP9) is a strong negative regulator of transcription factor activating kinases (ERK, JNK and p38) in the mitogen-activated protein kinase (MAPK) pathways. The aim of this study was to examine the CpG island methylation status of DUSP9 using bisulfite sequencing PCR (BSP) in gastric cancer (GC). The investigation was conducted on 30 clinical GC samples and selected corresponding tumor-free normal gastric mucosa tissues, using BSP for the determination of the… 

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References

SHOWING 1-10 OF 33 REFERENCES
Protein inhibitor of activated STAT-1 is downregulated in gastric cancer tissue and involved in cell metastasis.
TLDR
It is suggested that PIAS1 may function as a tumor suppressor to regulate gastric cancer cell metastasis by targeting the MAPK signaling pathway.
Development of a DUSP9 Methylation Screening Assay
TLDR
No CIMP features were found for the weakly methylated samples analyzed in this study but could be seen in 82 % of the strongly methylated cases, indicating a possible use for DUSP9 (dual-specificity phosphatase 9) as C IMP marker.
Microtubule disruption and tumor suppression by mitogen-activated protein kinase phosphatase 4.
TLDR
MKP4, a cytosolic MKP with specificity to not only Erk, but also, to a lesser extent, c-jun-NH(2)-kinase and p38, provides a novel mechanism for tumor suppression and implies a novel therapeutic strategy through combined MAPK inhibitions that mimic the function of MKP4.
Decreased Expression and Prognostic Role of Mitogen-Activated Protein Kinase Phosphatase 4 in Hepatocellular Carcinoma
TLDR
MKP-4 expression was downregulated in HCC tissues and proliferating HCC cells and correlated with OS and TTR, which suggested that MKP- 4 is a candidate prognostic marker for HCC.
Reduced BMP6 expression by DNA methylation contributes to EMT and drug resistance in breast cancer cells.
TLDR
Data indicated that hypermethylation modifications contributed to the regulation of BMP6 and induced an EMT phenotype of breast cancer during the acquisition of drug resistance.
β-Ionone arrests cell cycle of gastric carcinoma cancer cells by a MAPK pathway
Abstractβ-Ionone is an end ring analog of β-carotenoid which has been shown to possess potent anti-proliferative activity both in vitro and in vivo. To investigate the possible inhibitory effects of
Role of mitogen-activated protein kinase phosphatases (MKPs) in cancer
  • Gen Sheng Wu
  • Biology, Chemistry
    Cancer and Metastasis Reviews
  • 2007
TLDR
It is suggested that MKPs play an important role not only in the development of cancers, but also in the response of cancer cells to chemotherapy, and their impact on chemotherapy can be exploited for therapeutic benefits.
Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma
TLDR
It is found that decreased expression of DUSP-9 is associated with poor prognosis in ccRCC and may represent a novel and useful prognostic marker forccRCC.
Dual-specificity MAP kinase phosphatases (MKPs) and cancer
  • S. Keyse
  • Biology
    Cancer and Metastasis Reviews
  • 2008
TLDR
The current evidence implicating the dual-specificity MKPs in the initiation and development of cancer and also on the outcome of treatment is summarized.
Differential promoter methylation of kinesin family member 1a in plasma is associated with breast cancer and DNA repair capacity
TLDR
This work isolated plasma DNA from 340 participants in a breast cancer case control project to study promoter methylation levels of five genes previously shown to be associated with breast cancer in frozen tissue and in cell line DNA, finding the first evidence of a significant association between genetic and epigenetic alterations in breast cancer using blood-based tests.
...
...