The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via β-catenin/Cdc25c signaling and G2/M arrest

@article{Zhang2018TheN6,
  title={The new 6q27 tumor suppressor DACT2, frequently silenced by CpG methylation, sensitizes nasopharyngeal cancer cells to paclitaxel and 5-FU toxicity via $\beta$-catenin/Cdc25c signaling and G2/M arrest},
  author={Yan Zhang and Jiangxia Fan and Yichao Fan and Lili Li and Xiaoqian He and Qin Xiang and Junhao Mu and Danfeng Zhou and Xuejuan Sun and Yucheng Yang and Guosheng Ren and Q. Tao and Tingxiu Xiang},
  journal={Clinical Epigenetics},
  year={2018},
  volume={10}
}
BackgroundNasopharyngeal carcinoma (NPC) is prevalent in South China, including Hong Kong and Southeast Asia, constantly associated with Epstein-Barr virus (EBV) infection. Epigenetic etiology attributed to EBV plays a critical role in NPC pathogenesis. Through previous CpG methylome study, we identified Disheveled-associated binding antagonist of beta-catenin 2 (DACT2) as a methylated target in NPC. Although DACT2 was shown to regulate Wnt signaling in some carcinomas, its functions in NPC… 
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TLDR
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TLDR
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TLDR
DACT2 is frequently methylated in human gastric cancer and DACT2 expression is silenced by promoter region hypermethylation, which is associated with tumor differentiation, invasion and intravascular cancerous emboli.
Characterization of the nasopharyngeal carcinoma methylome identifies aberrant disruption of key signaling pathways and methylated tumor suppressor genes.
TLDR
The NPC methylome shows a special high-degree CpG methylation epigenotype, similar to the Epstein-Barr virus-infected gastric cancer, indicating a critical epigenetic etiology for NPC pathogenesis.
The Tumor Suppressor UCHL1 Forms a Complex with p53/MDM2/ARF to Promote p53 Signaling and Is Frequently Silenced in Nasopharyngeal Carcinoma
TLDR
It is indicated that UCHL1 could deubiquitinate p53 and p14ARF and ubiquitinate MDM2 for p53 stabilization to promote p53 signaling, thus involved in nasopharyngeal carcinoma pathogenesis, whereas it is frequently silenced in this tumor.
DACT1, an antagonist to Wnt/β-catenin signaling, suppresses tumor cell growth and is frequently silenced in breast cancer
TLDR
Functional assays showed that ectopic expression of DACT1 could inhibit breast tumor cell proliferation in vivo and in vitro through inducing apoptosis, and further suppress tumor cell migration through antagonizing the Wnt/β-catenin signaling pathway.
DACT2 silencing by promoter CpG methylation disrupts its regulation of epithelial-to-mesenchymal transition and cytoskeleton reorganization in breast cancer cells
TLDR
The results demonstrate that DACT2 functions as a tumor suppressor for breast cancer but was frequently disrupted epigenetically in this cancer.
DACT2 is a functional tumor suppressor through inhibiting Wnt/β-catenin pathway and associated with poor survival in colon cancer
TLDR
DACT2 acts as a functional tumor suppressor in colon cancer through inhibiting Wnt/β-catenin signaling and is significantly associated with shortened survival in stage I–III colon cancer patients.
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TLDR
This is the first report that a widely expressed protocadherin can also function as a TSG that is frequently inactivated epigenetically in multiple carcinomas.
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DACT2 suppresses HCC by inhibiting Wnt signaling in human HCC and its expression is regulated by promoter hypermethylation.
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TLDR
This study identified PCDH20 as a functional tumor suppressor and an important antagonist of Wnt/β‐catenin signaling and EMT, with frequent epigenetic inactivation in NPC.
Protocadherin8 is a functional tumor suppressor frequently inactivated by promoter methylation in nasopharyngeal carcinoma
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TLDR
For the first time, this study demonstrates the epigenetic inactivation of PCDH8 by promoter methylation and its tumor-suppressive function in NPC, which could be identified as a tumor suppressor in NPC.
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