Vitamin D Intake Is Negatively Associated with Promoter Methylation of the Wnt Antagonist Gene<i>DKK1</i>in a Large Group of Colorectal Cancer Patients

Rawson, James B.; Sun, Zhonghua; Dicks, Elizabeth; Daftary, Darshana; Parfrey, Patrick S.; Green, Roger C.; Gallinger, Steven; McLaughlin, John; Knight, Julia A.; Bapat, Bharati

doi:10.1080/01635581.2012.711418

Cited by 52 publications

(38 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The silencing of DKK-1 expression has been related to histone deacetylation and DNA hypermethylation (45,46). Recent studies also indicated the possible association of histone methylation with DKK-1 expression.…”

Section: Discussionmentioning

confidence: 99%

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

et al. 2014

View full text Add to dashboard Cite

Polycomb protein chromobox homolog 7 (CBX7) is involved in several biologic processes including stem cell regulation and cancer development, but its roles in breast cancer remain unknown. Here, we demonstrate that CBX7 negatively regulates breast tumor initiation. 2 /ESA + cell population and reinforced in vitro self-renewal and in vivo tumor-initiating ability. Similarly, CBX7 overexpression repressed these effects. We also found that CBX7 inhibits the Wnt/b-catenin/T cell factor pathway by enhancing the expression of Dickkopf-1 (DKK-1), a Wnt antagonist. In particular, CBX7 increased DKK-1 transcription by cooperating with p300 acetyltransferase and subsequently enhancing the histone acetylation of the DKK-1 promoter. Furthermore, pharmacologic inhibition of DKK-1 in CBX7-overexpressing cells showed recovery of Wnt signaling and consequent rescue of the CD44 +

show abstract

Section: Discussionmentioning

confidence: 99%

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Notably, DKK1 methylation was found to be a robust marker for the prediction of recurrence in stage II colon cancer patients [36]. It is reported that dietary vitamin D intake was strongly negatively associated with DKK1 methylation and may alter colon cancer risks [11]. These modulations by T3E might be a valuable strategy to overcome the therapeutic resistance of MM [37, 38].…”

Section: Discussionmentioning

confidence: 99%

“…In a large cohort study of colorectal cancer patients, vitamin D intake was negatively associated with DKK1 promoter methylation [11]. It is thought that vitamin E, which possesses anti-cancer properties, also affects epigenetic factors [12].…”

Section: Introductionmentioning

confidence: 99%

A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells

et al. 2018

View full text Add to dashboard Cite

Background: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1). Methods: WST-1 and cell analyzers were employed to analyze the effects of T3E on cell viability and apoptosis of human MM cell lines (H2452, H28). Real-time PCR and Western blot were performed to evaluate the expression at mRNA and protein levels. Methylation status and epigenetic modifications of DKK1’s promoter regions after T3E treatment in MM cells were studied using methylation-specific PCR and Chromatin immunoprecipitation. Small interfering RNA-mediated knockdown (siRNA), and specific inhibitors, were used to validate DKK1 as a target of T3E. Results: T3E markedly impaired MM cell viability, increased the expression of phosphorylated-JNK and DKK1 and suppressed cyclin D, a downstream target gene of Wnt signaling. Knockdown of DKK1 expression by siRNA or a specific JNK inhibitor confirmed the contribution of DKK1 and JNK to T3E-induced cytotoxicity in MM cells. On the other hand, cytoskeleton-associated protein 4 (CKAP4) expression, which promotes cell proliferation as a Wnt-independent DKK1 receptor was inhibited by T3E. Silencing CKAP4 by siRNA did not appear to directly affect MM cell viability, thereby indicating that expression of both DKK1 and CKAP4 is required. Furthermore, T3E-mediated inhibition of both DNA methyltransferases (DNMT1, 3A, and 3B) and histone deacetylases (HDAC1, 2, 3, and 8) in MM cells leads to increased DKK1 expression, thereby promoting tumor growth inhibition. MM cells treated with Zebularine (a DNMT inhibitor) and sodium butyrate (an HDAC inhibitor) exhibited cytotoxic effects, which may explain the inhibitory action of T3E on MM cells. In addition, an enhanced expression of DKK1 in MM cells following T3E treatment is positively correlated with the methylation status of its promoter; T3E decreased DNA methylation and increased histone acetylation. Moreover, T3E specifically increased histone H3 lysine 4 (H3K4) methylation activity, whereas no effects were observed on histone H3K9 and H3K27. Conclusions: Targeting the epigenetic induction of DKK1 may lead to effective treatment of MM, and T3E has great potential to induce anti-MM activity.

show abstract

“…Histone modification and promoter CpG methylation alter cancer-related gene expression and are frequently involved in carcinogenesis [58] . So far, downregulation of Wnt antagonist genes associated to promoter hypermethylation have been identified in a variety of malignancies, such as renal, bladder, lung, breast, colorectal, gastric and neuroblastoma [59][60][61][62][63][64][65] . Furthermore, the Wnt/b-catenin pathway genes are found among those affected by dysregulation of microRNAs (miRNAs) in many kinds of cancers, and particularly, expression profiling has shown that certain miRNAs are associated with gastric cancer development, progression and response to therapy [66][67][68] .…”

mentioning

confidence: 99%

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Chiurillo

2015

WJEM

260

219

View full text Add to dashboard Cite

Gastric cancer remains one of the most common cancers worldwide and one of the leading cause for cancerrelated deaths. Gastric adenocarcinoma is a multifactorial disease that is genetically, cytologically and architecturally more heterogeneous than other gastrointestinal carcinomas. The identification of specific membrane, intracellular, and extracellular components of the Wnt pathway has revealed potential targets for gastric cancer therapy. High-throughput "omics" approaches will help in the search for Wnt pathway antagonist in the near future.

show abstract

Vitamin D Intake Is Negatively Associated with Promoter Methylation of the Wnt Antagonist GeneDKK1in a Large Group of Colorectal Cancer Patients

Cited by 52 publications

References 32 publications

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

CBX7 inhibits breast tumorigenicity through DKK‐1‐mediated suppression of the Wnt/β‐catenin pathway

A Succinate Ether Derivative of Tocotrienol Enhances Dickkopf-1 Gene Expression through Epigenetic Alterations in Malignant Mesothelioma Cells

Role of the Wnt/β-catenin pathway in gastric cancer: An in-depth literature review

Contact Info

Product

Resources

About