Aberrant promoter methylation of <scp>D</scp>ab2 gene in myelodysplastic syndrome

Yang, Yujuan; Zhang, Qingxia; Xu, Feng; Chang, Chunkang; Xiao, Li

doi:10.1111/ejh.12014

Cited by 6 publications

(4 citation statements)

References 48 publications

(62 reference statements)

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“…Our study demonstrated that the methylation of Dab2 is common in lung cancers, similar to the reports in other tumors (23,(28)(29)(30). Furthermore, the methylation of Dab2 was correlated with the differentiation, lymphatic metastasis, and TNM stage of lung cancers.…”

Section: Discussionsupporting

confidence: 88%

Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers

Xie

Zhang

Yang

et al. 2013

International Journal of Oncology

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Disabled-2 (Dab2) is considered a tumor suppressor and is downregulated in cancers. We examined the promoter methylation status and expression levels of Dab2, and investigated their roles in the development of lung cancers. Methylation-specific PCR was employed to analyze the methylation status of Dab2 in 100 lung cancer tissues. The cytoplasmic and nuclear expression of the Dab2 protein was determined using western blot analysis. Demethylation treatment using 5-Aza-2-deoxycytidine (5-Aza-dC) was performed in three lung cancer cell lines. Dab2 expression was upregulated by Dab2 transfection or interrupted by Dab2 siRNA in lung cancer cells. Proliferative and invasive ability tests were performed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTS) and a Matrigel invasion assay, respectively. The methylation rate of Dab2 was significantly higher in lung cancer tissues compared to normal lung tissues. Dab2 methylation correlated with the reduced nuclear and cytoplasmic expression of Dab2, as well as the TNM stage and lymphatic metastasis of lung cancers. Treatment with 5-Aza-dC was able to eliminate the hypermethylation of Dab2, enhance Dab2 expression, and inhibit β-catenin expression, and the proliferative and invasive ability of lung cancer cells. Upregulation of Dab2 expression reduced β-catenin expression and proliferation and invasiveness of lung cancer cells. However, interruption of Dab2 expression induced the opposite results. Dab2 methylation is common in lung cancers, and is one of the most important factors responsible for the reduced expression of Dab2. Aberrant hypermethylation and reduced expression of Dab2 promote the development of lung cancers.

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Section: Discussionsupporting

confidence: 88%

Aberrant hypermethylation and reduced expression of disabled-2 promote the development of lung cancers

Xie

Zhang

Yang

et al. 2013

International Journal of Oncology

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“…Likewise, ectopic expression of Dab2 in several tumor cell lines triggered negative cell growth regulatory properties and tumor suppressive activity of the protein in these cells [22,30]. Downregulation or loss of expression of Dab2 has been correlated with its abnormal promoter hypermethylation [31][32][33][34][35][36] and the presence of inhibitory microRNAs [31,[37][38][39] in human cancers. Despite these findings, additional studies are necessary to better understand the correlation between Dab2 gene silencing and cancer development.…”

Section: Disabled-2 a Putative Tumor Suppressormentioning

confidence: 99%

“…Downregulation or loss of expression of Dab2 has been correlated with its abnormal promoter hypermethylation [31][32][33][34][35][36] and the presence of inhibitory microRNAs [31,[37][38][39] in human cancers. Despite these findings, additional studies are necessary to better understand the correlation between Dab2 gene silencing and cancer development.…”

Section: Disabled-2 a Putative Tumor Suppressormentioning

confidence: 99%

Disabled-2: A modular scaffold protein with multifaceted functions in signaling

Finkielstein

Capelluto

2015

Inside the Cell

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Disabled‐2 (Dab2) is a multimodular scaffold protein with signaling roles in the domains of cell growth, trafficking, differentiation, and homeostasis. Emerging evidences place Dab2 as a novel modulator of cell–cell interaction; however, its mode of action has remained largely elusive. In this review, we highlight the relevance of Dab2 function in cell signaling and development and provide the most recent and comprehensive analysis of Dab2's action as a mediator of homotypical and heterotypical interactions. Accordingly, Dab‐2 controls the extent of platelet aggregation through various motifs within its N‐terminus. Dab2 interacts with the cytosolic tail of the integrin receptor blocking inside‐out signaling, whereas extracellular Dab2 competes with fibrinogen for integrin αIIbβ3 receptor binding and, thus, modulates outside‐in signaling. An additional level of regulation results from Dab2's association with cell surface lipids, an event that defines the extent of cell–cell interactions. As a multifaceted regulator, Dab2 acts as a mediator of endocytosis through its association with the [FY]xNPx[YF] motifs of internalized cell surface receptors, phosphoinositides, and clathrin. Other emerging roles of Dab2 include its participation in developmental mechanisms required for tissue formation and in modulation of immune responses. This review highlights the various novel mechanisms by which Dab2 mediates an array of signaling events with vast physiological consequences.

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“…Widespread promoter hypermethylation in MDS and secondary AML has been reported by the recent study of Figueroa et al According to this study, bone marrow cells from patients with MDS and secondary AML exhibit an extensive pattern of promoter hypermethylation that differs from normal cells and de novo AML and is not limited with advanced stages of disease. 15 Another gene whose methylation is implicated in MDS pathogenesis is the erythroid transcription factor GATA1, whose upregulation is necessary for erythroid and megakaryocytic development. Methylation of GATA1 in MDS patients inhibits upregulation of the gene and leads to ineffective erythropoiesis.…”

Section: Dna Methylationmentioning

confidence: 99%