Expression and epigenetic regulation of DACT1 and DACT2 in oral squamous cell carcinoma

Schussel, Juliana Lucena; Kalinke, Luciana Puchalski; Sassi, Laurindo Moacir; Oliveira, Benedito Valdecir de; Pedruzzi, P.A.G.; Olandoski, Márcia; Alvares, Lúcia Elvira; Garlet, Gustavo; Trevilatto, Paula Cristina

doi:10.3233/cbm-140436

Cited by 17 publications

(16 citation statements)

References 40 publications

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“…Downregulation or epigenetic silencing of this gene results in dysregulation of these pathways resulting in carcinogenesis. 15 HOXD10 was significantly upregulated in all 3 comparisons in our samples. It has been shown that high expression of HOXD10 gives cancer cells a proliferative and migratory advantage whereas low expression may support invasion and metastasis.…”

Section: Discussionmentioning

confidence: 69%

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Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

et al. 2018

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Background The objective was to study comprehensive mRNA expression profiles of buccal mucosa oral squamous cell carcinoma (OSCC‐BM) and gingivo‐buccal OSCC (OSCC‐GB) in smokeless tobacco chewers to understand the biological behavior of OSCC at these specific sites and identify diagnostic and prognostic markers. Methods High throughput RNA sequencing transcriptome of fresh buccal mucosa (4 samples) and gingivo‐buccal (4 samples) OSCC with normal oral mucosa (3 samples) was performed on Illumina NextSeq500 paired end sequencing with 75x2bp. Results In the comparison between OSCC and normal, there were 402 differentially expressed genes (DEGs); between OSCC‐BM and normal, there were 467 DEGs; and between OSCC‐GB and normal oral tissue, there were 608 DEGs. Pathway‐based analysis of gene expression was done. The inflammation mediated by chemokine and cytokine signaling pathway had the maximum gene hits. Conclusions FZD2 and its interactions with the cadherins have a role in invasion and metastasis. immunosurveillance is evident in OSCC‐GB with the downregulation of CADM1.

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Section: Discussionmentioning

confidence: 69%

“…DACT2 gene regulates the TGF B pathway and Wnt pathway. Downregulation or epigenetic silencing of this gene results in dysregulation of these pathways resulting in carcinogenesis . HOXD10 was significantly upregulated in all 3 comparisons in our samples.…”

Section: Discussionmentioning

confidence: 73%

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

et al. 2018

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“…In addition to deletion, epigenetic modifications of DACT genes were also reported. For instance, DACT1 and DACT2 were reported to be methylated in hepatocellular carcinoma, oral squamous, gastric cancer, nasopharyngeal carcinoma, thyroid cancer, colon cancer and lung cancer (10,(26)(27)(28)(29)(30)(31). In addition, DACT3 was identified to have histone modifications in colorectal cancer (25,26,32).…”

Section: Discussionmentioning

confidence: 99%

Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Wang

Yang

et al. 2017

Oncol Lett

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Abstract. The activation of the Wnt/β-catenin signaling pathway has been demonstrated to play important roles in breast carcinogenesis and to be associated with a poorer prognosis in breast cancer patients. However, genetic mutation is not the major reason for Wnt/β-catenin activation in breast cancer. Dishevelled-associated antagonist of β-catenin homolog 2 (DACT2) is a negative regulator of β-catenin and acts as a tumor suppressor in numerous cancer types; however, the expression change and potential role of DACT2 in breast cancer is unknown. The present study detected the expression and function of DACT2 in breast cancer progression. It was identified that the expression of DACT2 significantly decreased in breast cancer tissues compared with paired adjacent normal breast tissues. Additional investigation demonstrated that the hypermethylation of DACT2 gene promoter contributes to the loss of the gene in breast cancer. It was also demonstrated that DACT2 is a tumor suppressor in breast cancer and inhibits the proliferation and invasion of breast cancer cells by repressing the expression of β-catenin target genes associated with tumor growth and metastasis. The present study indicates that the loss of DACT2 may contribute to breast cancer progression and provides a promising therapeutic target for the treatment of breast cancer.

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“…In addition, decreased expression and promoter hypermethylation of DACT1 and DACT2 have been found in some primary tumors and tumor cell lines, including hepatocellular carcinoma [15], breast cancer [16], lung cancer [17], colorectal cancer [18] and some other cancers. However, Schussel et al [19] showed quite a different result which the promoter methylation of DACT1 and DACT2 may not be a common event in oral squamous cell carcinoma. Although the promoter of DACT3 also has a large CpG Island, but the study in colorectal cancer indicates that the histone modification, rather than the aberrant, may be the main regulated mechanism for inactivation of this gene [18].…”

Section: Introductionmentioning

confidence: 99%

Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma

et al. 2017

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BackgroundThe DACT (Dishevelled-associated antagonist of β-catenin) family of scaffold proteins may play important roles in tumorigenesis. However, the epigenetic changes of DACT1, 2, 3 and their effect on esophageal squamous cell carcinoma (ESCC) have not been investigated so far. The aim of this study was to investigate the promoter methylation and expression of DACT family, in order to elucidate more information on the role of DACT with regard to the progression and prognosis of ESCC.MethodsMSP and BGS methods were respectively applied to examine the methylation status of DACT; RT-PCR, Western blot and immunohistochemistry methods were respectively used to determine the mRNA and protein expression of DACT; MTT, Colony-formation and Wound-healing assay were performed to assess the effect of DACT1 and DACT2 on proliferation and migration of esophageal cancer cells.ResultsFrequent reduced expression of DACT1, DACT2 and DACT3 were found in esophageal cancer cell lines and the expression levels of DACT1 and DACT2 were reversed by 5-Aza-Dc. Decreased mRNA and protein expression of DACT1 and DACT2 were observed in ESCC tumor tissues and were associated with the methylation status of transcription start site (TSS) region. The hypermethylation of CpG islands (CGI) shore region in DACT1 was observed both in tumor and corresponding adjacent tissues but wasn’t related to the transcriptional inhibition of DACT1. The methylation status of TSS region in DACT1 and DACT2 and the protein expression of DACT2 were independently associated with ESCC patients’ prognosis.ConclusionsThe TSS region hypermethylation may be one of the main mechanisms for reduced expression of DACT1 and DACT2 in ESCC. The simultaneous methylation of DACT1 and DACT2 may play important roles in progression of ESCC and may serve as prognostic methylation biomarkers for ESCC patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12929-016-0308-6) contains supplementary material, which is available to authorized users.

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Expression and epigenetic regulation of DACT1 and DACT2 in oral squamous cell carcinoma

Cited by 17 publications

References 40 publications

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

Pathway based prognostic gene expression profile of buccal and gingivo‐buccal oral squamous cell carcinoma in smokeless tobacco chewers

Methylation of DACT2 contributes to the progression of breast cancer through activating WNT signaling pathway

Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma

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