Induction and Down-regulation of Sox17 and Its Possible Roles During the Course of Gastrointestinal Tumorigenesis

Du, You Wei; Oshima, Hiroko; Oguma, Koichi; Kitamura, Takanori; Itadani, Hiraku; Fujimura, Takashi; Piao, Yingshi; Yoshimoto, Tanihiro; Minamoto, Toshinari; Kotani, Hidehito; Taketo, Makoto Mark; Oshima, Masanobu

doi:10.1053/j.gastro.2009.06.041

Cited by 62 publications

(48 citation statements)

References 35 publications

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“…We have chosen to first study CST6, BRMS1, and SOX17 gene methylation in CTCs, after a very careful search in the literature, since the available material for CTC analysis is extremely low. These 3 genes, as already established through other studies in cell lines and primary tumors, each play an important role in preventing metastasis (18,19,25,27,28,30 ). Methylation of their promoters is highly correlated with their epigenetic silencing, development of metastasis, and poor prognosis (21,23,24,26,29 ).…”

Section: Discussionmentioning

confidence: 97%

“…Similarly, SOX17 plays a critical role in the regulation of development and stem/precursor cell function, at least partly through repression of Wnt pathway activity (30 ). SOX17 has been shown to alter adult lung progenitor cell fate, decrease the expression of transforming growth factor-␤ (TGF-␤)-responsive cell cycle inhibitors, and inhibit TGF-␤1-mediated transcriptional responses in vitro, while blocking Smad3 DNA binding and transcriptional activity (40 ).…”

Section: Discussionmentioning

confidence: 99%

“…SOX17 gene silencing is associated with DNA hypermethylation of a C-phosphate-G (CpG) island located in the promoter region (29 ). It is well established that SOX17 plays a tumor suppressor role through suppression of Wnt signaling (30 ).…”

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confidence: 99%

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DNA Methylation of Tumor Suppressor and Metastasis Suppressor Genes in Circulating Tumor Cells

et al. 2011

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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DNA Methylation of Tumor Suppressor and Metastasis Suppressor Genes in Circulating Tumor Cells

et al. 2011

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“…These molecular changes seem to be required to drive early carcinogenesis events in the stomach, a hypothesis that is supported by studies showing that GSK3b phosphorylation and inactivation is associated with cancer progression in gastric cancer [105] . Different studies have shown downregulation-in occasion by unspecified mechanisms-of various negative regulators of the Wnt/b-catenin signaling involved in proliferation and invasion in gastric cancer, including sFRP, Sox7, Sox10, Sox17, HSulf-1, RACK1, ZNRF3 and OSR1 [78,[106][107][108][109][110][111][112][113] . Some Wnt-target genes, such as Dkk-1, Axin, Nemo kinase, etc., have shown to cause inhibition of Wnt signaling itself [114,115] .…”

Section: Loss Of Wnt Repressor Function In Gastric Cancermentioning

confidence: 99%

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

Chiurillo

2015

WJEM

252

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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.

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“…SOX17, a member of the Sry-related high mobility group box (SOX) family of transcription factors, is conserved in many species and plays critical roles in the regulation of development and stem/precursor cell function, at least partly through repression of the canonical Wnt/␤-catenin signaling pathway (15,16 ). Global analysis of CpG island hypermethylation and gene expression in colorectal cancer cell lines has revealed that SOX17 gene silencing is associated with DNA hypermethylation (17 ), and SOX17 plays a tumor suppressor role through suppression of Wnt signaling (18 ).…”

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confidence: 99%

SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer

et al. 2013

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INTRODUCTION Detection of circulating tumor cells (CTCs) and cell-free DNA (cfDNA) in the peripheral blood of patients with solid tumors has been widely studied for the early detection of metastatic spread. We evaluated whether there was an association between the origin of cfDNA and CTCs. We investigated whether SRY (sex determining region Y)-box 17 (SOX17) promoter methylation in CTCs was associated with the methylation pattern of this gene in matched cfDNA isolated from plasma of patients with breast cancer. METHODS We examined SOX17 methylation in 79 primary breast tumors, in 114 paired samples of DNA isolated from CTCs and cfDNA, and in 60 healthy individuals. Isolated DNA was modified by sodium bisulfite and subjected to methylation specific PCR. RESULTS The SOX17 promoter was methylated in 68 (86.0%) of 79 of primary breast tumors. In CTCs, SOX17 was methylated in 19 (34.5%) of 55 patients with early breast cancer, 27 (45.8%) of 59 patients with metastatic cancer, and 1 (4.3%) of 23 healthy individuals, whereas in matched cfDNA SOX17 was methylated in 19 (34.5%) of 55, 24 (40.7%) of 59, and 1 (2.0%) of 49 of these same groups, respectively. There was a significant correlation between SOX17 methylation in cfDNA and CTCs in patients with early breast cancer (P = 0.008), but not in patients with verified metastasis (P = 0.283). CONCLUSIONS The SOX17 promoter is highly methylated in primary breast tumors, in CTCs isolated from patients with breast cancer, and in corresponding cfDNA samples. Our findings indicate a direct connection between the presence of CTCs and cfDNA in patients with operable breast cancer, after surgical removal of the primary tumor.

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Induction and Down-regulation of Sox17 and Its Possible Roles During the Course of Gastrointestinal Tumorigenesis

Cited by 62 publications

References 35 publications

DNA Methylation of Tumor Suppressor and Metastasis Suppressor Genes in Circulating Tumor Cells

DNA Methylation of Tumor Suppressor and Metastasis Suppressor Genes in Circulating Tumor Cells

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

SOX17 Promoter Methylation in Circulating Tumor Cells and Matched Cell-Free DNA Isolated from Plasma of Patients with Breast Cancer

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