Claudin-6, 7, or 9 Overexpression in the Human Gastric Adenocarcinoma Cell Line AGS Increases Its Invasiveness, Migration, and Proliferation Rate

Zavala‐Zendejas, Veronica Elizabeth; Torres-Martínez, Ana C.; Salas‐Morales, Berenice; Fortoul, Teresa I.; Montaño, Luis F.; Rendón-Huerta, Erika P.

doi:10.3109/07357907.2010.512594

Cited by 86 publications

(69 citation statements)

References 47 publications

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“…They also found that knockdown of claudin 1 increased the tumorigenicity of human gastric cancer cells (12). However, study also found that overexpression of other members of claudin (CLDN6, 7 and 9) in gastric cancer cells increased the invasiveness, migration and proliferation (37).…”

Section: Discussionmentioning

confidence: 95%

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

Huang

et al. 2014

International Journal of Oncology

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Abstract. Claudin 1 is one of the tight junction proteins, which are critical in the maintenance of epithelial integrity. Aberrant regulation of CLDN1 and its correlation with β-catenin have been discovered in malignant tumors. The present study aimed to investigate the expression profile and clinical relevance of CLDN1 and β-catenin. The protein levels of CLDN1 and β-catenin were examined using immunohistochemical staining. The characteristics of expression profile and prognostic value were analyzed using Pearson's χ 2 test and Kaplan-Meier analysis, respectively. β-catenin overexpression and knockdown were used to investigate its role in regulating CLDN1 expression. We showed that CLDN1 was overexpressed in intestinal-type, presence of lymph node metastasis, higher TNM stage in gastric cancer patients and correlated with decreased overall survival. The characteristics of CLDN1 expression were associated with that of β-catenin. CLDN1 and β-catenin showed similar prognostic value in intestinal-type gastric cancers. β-catenin knockdown and overexpression in cell models revealed a positive relation between CLDN1 and β-catenin. Our study demonstrated that CLDN1 is a biomarker for intestinal-type gastric cancer with shorter survival. The expression of CLDN1 was strongly associated with β-catenin in gastric cancer patients and a gastric cancer cell model. IntroductionGastric cancer is the fourth most common cancer worldwide and is the second most common cause of cancer-related deaths.Gastric cancer has a poor prognosis (1). Although the 5-year survival rate in patients with early-stage disease is ~90%, since the vast majority present with distant metastasis, the overall 5-year survival rate is typically <20% (2). The 5-year survival rate has also been significantly correlated with the degree of tumor invasion, the presence of lymph node and/ or distant metastases and the TNM stage (3,4). However, very limited number of molecules that have clinicopathological significance in gastric cancer has been discovered.Claudin 1 (CLDN1) is one of the integral membrane proteins that constitute tight junctions. Tight junctions are essential for the tight sealing of cellular sheets and maintaining homeostasis (5). Absence of tight junctions or defective tight junctions is associated with the development of the neoplastic phenotype in epithelial cells (6). Thus it is accepted that the disruption of tight junctions leads to loss of cohesion, invasiveness and the lack of differentiation, thereby promoting tumorigenesis. CLDN1 is found to regulate intestinal epithelial homeostasis through the modulation of Notch-signaling (7). Many chemicals and nutrition can regulate CLDN1 expression through different pathways (8,9) to maintain the integrity of intestinal barrier function.The complexity of CLDN1 was proposed because its dual role as a tumor suppressor and promoter, as well as a positive and negative prognostic factor in different cancers, including breast (10,11), gastric (12), ovarian (13), lung (14) and colon (15-17). Decreased exp...

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Section: Discussionmentioning

confidence: 95%

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

Huang

et al. 2014

International Journal of Oncology

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“…Cldn6, a member of the tight junction family, has been reported to play an important role during mouse embryonic epithelium formation [4] and the development of endodermal tissues [5]. The level of Cldn6 expression is correlated with dedifferentiation and malignant proliferation of epithelial cells [6,7]. However, little is known about the characteristics and function of Cldn6 in mouse PSCs [8].…”

Section: Dear Editormentioning

confidence: 99%

Claudin 6: a novel surface marker for characterizing mouse pluripotent stem cells

et al. 2012

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“…Increased expression of claudin-6, -7 and -9 is sufficient to enhance tumorigenic properties of a gastric adenocarcinoma cell line (Zavala-Zendejas et al, 2011). Claudin-1 is not expressed in the epithelium of normal canine colorectal mucosa, but increased expression of this protein was observed in canine low-grade colorectal adenocarcinoma (Jakab et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Expression of claudins in the normal canine gastric mucosa

Psáder

Jakab

Máthé

et al. 2014

Acta Veterinaria Hungarica

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The aim of the present study was to investigate the expression pattern of claudin-1, -2, -3, -4, -5, -6, -7, -8, -10 and -18 in the intact fundic and pyloric gastric mucosa of dogs. Intense, linear, membranous claudin-18 positivity was detected in the surface gastric cells and in the epithelial cells of the gastric glands both in the fundic and pyloric stomach regions. The mucous neck cells in the apical part of the glands, furthermore the parietal cells and chief cells of the basal part of the gland were all positive for claudin-18, in the same way as the enteroendocrine cells. Cells of the basal part of the pyloric glands showed intense, linear, membranous claudin-2 positivity, but cells of the superficial portion of these glands and the surface gastric cells in this region were claudin-2 negative. Fibroblasts, endothelial cells, lymphocytes of the propria layer, smooth muscle cells and vegetative neurons were all negative for claudin-2. All gastric epithelial cells were negative for claudin-1, -3, -4, -5, -6, -7, -8 and -10. The endothelial cells of the propria layer had intense claudin-5 positivity. We assume that claudin-18 forms a paracellular barrier against gastric acid in the healthy canine stomach, in the same way as in mice.

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Claudin-6, 7, or 9 Overexpression in the Human Gastric Adenocarcinoma Cell Line AGS Increases Its Invasiveness, Migration, and Proliferation Rate

Cited by 86 publications

References 47 publications

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

The expression of Claudin 1 correlates with β-catenin and is a prognostic factor of poor outcome in gastric cancer

Claudin 6: a novel surface marker for characterizing mouse pluripotent stem cells

Expression of claudins in the normal canine gastric mucosa

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