Pathophysiology of intestinal metaplasia of the stomach: emphasis on <i>CDX2</i> regulation

Barros, Rita; Camilo, Vânia; Pereira, Bruno; Freund, Jean–Noël; David, Leonor; Almeida, Raquel

doi:10.1042/bst0380358

Cited by 22 publications

(17 citation statements)

References 75 publications

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“…S1). This expression pattern indicated that, with respect to intestinal metaplasia, uninfected GCIY cells are similar to epithelial cells of the gastric mucosa not infected by H. pylori (3, 16). In contrast, AGS, NUGC-4, and KATOIII cells expressed Cdx2 and MUC2 prior to infection with H. pylori .…”

Section: Resultsmentioning

confidence: 82%

“…The occurrence of gastric intestinal metaplasia during H. pylori infection has been reported to be dependent on induction of Cdx2 expression in gastric epithelial cells (3). Thus, in initial studies, we evaluated Cdx2 expression and other epithelial cell differentiation markers in human gastric cancer cell lines before and after infection with H. pylori.…”

Section: Resultsmentioning

confidence: 99%

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Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

et al. 2016

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Chronic infection with the bacterial Helicobacter pylori is a major cause of gastric and duodenal ulcer disease, gastric mucosal atrophy, and cancer. H. pylori–induced expression of the intestinal epithelial–specific transcription factor caudal-related homeobox 2 (Cdx2) contributes to intestinal metaplasia, a precursor event to gastric cancer. Given a role for the bacterial pattern recognition molecule nucleotide-binding oligomerization domain 1 (NOD1) in the innate immune response to bacterial infection, we investigated mechanisms used by NOD1 to regulate H. pylori infection and its propensity towards the development of intestinal metaplasia. We found that Cdx2 was induced by H. pylori infection in both normal and neoplastic gastric epithelial cells in a manner that was inversely related to NOD1 signaling. Mechanistic investigations revealed that Cdx2 induction relied upon activation of NF-κB but was suppressed by NOD1-mediated activation of TRAF3, a negative regulator of NF-κB. In vivo, prolonged infection of NOD1-deficient mice with H. pylori led to increased Cdx2 expression and intestinal metaplasia. Furthermore, gastric epithelial cells from these mice exhibited increased nuclear expression of the NF-κB p65 subunit and decreased expression of TRAF3. Overall, our findings illuminated a role for NOD1 signaling in attenuating H. pylori–induced Cdx2 expression in gastric epithelial cells, suggesting a rationale to augment NOD1 signaling in H. pylori–infected patients to limit their risks of accumulating precancerous gastric lesions.

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Section: Resultsmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 99%

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

et al. 2016

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“…Overexpression of CDX2 arrests GC cells in the G0/G1 stage of the cell cycle and induces cell apoptosis. All the results showed that CDX2 is involved in the regulation of GC proliferation and metastasis (21). In conclusion, CDX2 is a cancer suppressor gene of GC.…”

Section: Discussionmentioning

confidence: 99%

microRNA-32 inhibits the proliferation and invasion of the SGC-7901 gastric cancer cell line in vitro

et al. 2013

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microRNAs (miRNAs) are a class of endogenously expressed, small non-coding RNAs, which suppress their target mRNAs at the post-transcriptional level. miRNAs play key roles in tumor metastasis. The aim of the present study was to investigate the expression of miRNA-32 (miR-32) on the biological behavior of the human gastric cancer cell line, SGC-7901. SGC-7901 cells were transfected with miR-32-mimic, miR-32-inhibitor and empty plasmid vectors using Lipofectamine™ 2000. The expression of GFP was observed by fluorescent microscopy and miR-32 gene expression was detected by quantitative polymerase chain reaction. The cell counting kit-8 assay was performed to evaluate the effect of miR-32 expression on cell proliferation in vitro. Alterations in the migration and metastatic potential of SGC-7901 cells, prior to and following miR-32 gene transfection, were assayed by cell chemotactic migration and invasion tests. The results of the current study showed that the proliferation rate of the transfected SGC-7901 cells overexpressing miR-32 is reduced and cell chemotactic migration and invasion potentials is markedly reduced following miR-32-mimic transfection (P<0.05). In addition, the results demonstrated that overexpression of miR-32 greatly inhibits the proliferation and decreases the migration and invasion capabilities of SGC-7901 cells in vitro.

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“…Intestinal-type cancer is thought to be related to environmental factors and is considered to evolve through well-characterized sequential stages that progress through chronic gastritis, atrophy, intestinal metaplasia, and dysplasia (4). The intestine-specific expression of the homeoprotein, Cdx2, makes it one of the most likely candidates to be involved in inducing intestinal metaplasia of the stomach (5,6).…”

Section: Introductionmentioning

confidence: 99%

PTEN expression and suppression of proliferation are associated with Cdx2 overexpression in gastric cancer cells

Bai

Shen

et al. 2013

International Journal of Oncology

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Abstract. The prognosis of gastric cancer (GC) is associated with Cdx2 and nuclear PTEN coexpression. This study aimed to determine the expression patterns of Cdx2 and PTEN in various GC tissues and cell lines to identify their relationship in GC. Immunohistochemistry was undertaken to assess the expression patterns of Cdx2 and PTEN in paraffin-embedded specimens of 228 GC patients who had undergone radical D2 gastrostomy with long-term follow-up. Cell growth and tumorigenicity were analyzed in the BGC823 cells with exogenous Cdx2 and any changes in the associated signaling pathways were interpreted in exogenous cdx2 expression and cdx2 knockdown. Cdx2 was found in the nuclei of GC cells in 43.4% (99/228) of the paraffin-embedded biopsies. A higher expression of nuclear PTEN was observed in 36.4% (83/228). Coexpression of Cdx2 and nuclear PTEN was detected in GC tumors (59/228, 25.9%) which correlated with the prognosis of advanced GC patients (p<0.001). The expression levels of Cdx2 and PTEN were variable in the different GC cell lines. However, the trends were similar between PTEN and Cdx2 in GC tissues and cell lines. High expression of Cdx2 and PTEN significantly reduced tumorigenicity in BGC823 cells compared with the empty vector control. Exogenous expression of Cdx2 triggered the upregulation of PTEN expression and decreased PI3K and pAkt expression and vice versa. The coexpression levels of PTEN and Cdx2 in GC tumors correlated with prognosis in GC patients. Cdx2 may play a role in the upregulation of PTEN by triggering PI3K/Akt inactivation in GC cells.

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Pathophysiology of intestinal metaplasia of the stomach: emphasis on CDX2 regulation

Cited by 22 publications

References 75 publications

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

Cdx2 Expression and Intestinal Metaplasia Induced by H. pylori Infection of Gastric Cells Is Regulated by NOD1-Mediated Innate Immune Responses

microRNA-32 inhibits the proliferation and invasion of the SGC-7901 gastric cancer cell line in vitro

PTEN expression and suppression of proliferation are associated with Cdx2 overexpression in gastric cancer cells

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