Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

Lu, Youzhu; Jing, Jingjing; Sun, Liping; Gong, Yuehua; Chen, Moye; Wang, Zeyang; Sun, Mingjun; Yuan, Yuan

doi:10.1371/journal.pone.0174476

Cited by 23 publications

(12 citation statements)

References 39 publications

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“…In addition, the expression of claudin-10 and claudin-17 was downregulated, while the expression of claudin-14 was upregulated, in gastric cancer tissues compared with in tumor adjacent tissues ( 48 ). The expression of claudin-11 and −23 was greatly increased in paracancerous gastric tissue compared with cancerous tissue ( 49 ). These results suggested that the functions of claudin proteins may be highly tissue-specific and may be the candidate biomarkers of gastric cancer progression.…”

Section: Discussionmentioning

confidence: 99%

Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Yang

Sun

2018

Mol Med Report

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Numerous genetic alterations associated with cancer progression have the potential to serve as biomarkers for the early diagnosis of cancer. Numerous studies have suggested that claudin proteins, which are the primary components of tight junction structures, are associated with the regulation of cell polarity and cell differentiation. To investigate the expression profiles of the tight junction proteins claudin-2, −5, −7 and −8 in gastric carcinoma, immunohistochemical analysis, western blotting and reverse transcription-quantitative polymerase chain reaction analysis was used to detect the expression profiles of these claudin proteins in gastric carcinoma tissues and in homologous non-neoplastic mucosal tissues. According to the present study, the expression levels of claudin-7 and claudin-8 were downregulated, while the expression of claudin-5 was upregulated in gastric carcinoma tissues compared with in non-neoplastic mucosal tissues. Additionally, no notable difference was observed between claudin-2 expression in gastric carcinoma tissues and non-neoplastic mucosae. Correlations between claudin-7 and −8 expression and lymphatic metastasis in gastric carcinoma tissues were additionally reported. In summary, the present study revealed the distinct expression profiles of claudin-5, −7 and −8 in non-neoplastic mucosal tissues and gastric carcinoma tissues. Furthermore, the expression of these claudin proteins was highly associated with metastatic progression and prognosis in patients with gastric carcinoma, and had predictive value for the metastasis and survival of patients with gastric carcinoma.

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Section: Discussionmentioning

confidence: 99%

Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Yang

Sun

2018

Mol Med Report

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“…Additionally, expression of CLDN11 and CLDN23 is downregulated in gastric cancer89 and miR-421 was implicated in regulating CLDN11 expression to promote the proliferation, invasion and metastasis of gastric cancer cells90 (table 2). In contrast, CLDN23 positive expression was associated with poor prognostic outcomes of patients with gastric cancer and may therefore serve as an independent predictor of patient survival.…”

Section: Tj Proteins and The Gi Tractmentioning

confidence: 99%

Tight junction proteins in gastrointestinal and liver disease

Zeisel

Dhawan

Baumert

2018

Gut

229

179

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Over the past two decades a growing body of evidence has demonstrated an important role of tight junction (TJ) proteins in the physiology and disease biology of GI and liver disease. On one side, TJ proteins exert their functional role as integral proteins of TJs in forming barriers in the gut and the liver. Furthermore, TJ proteins can also be expressed outside TJs where they play important functional roles in signalling, trafficking and regulation of gene expression. A hallmark of TJ proteins in disease biology is their functional role in epithelial-to-mesenchymal transition. A causative role of TJ proteins has been established in the pathogenesis of colorectal cancer and gastric cancer. Among the best characterised roles of TJ proteins in liver disease biology is their function as cell entry receptors for HCV—one of the most common causes of hepatocellular carcinoma. At the same time TJ proteins are emerging as targets for novel therapeutic approaches for GI and liver disease. Here we review our current knowledge of the role of TJ proteins in the pathogenesis of GI and liver disease biology and discuss their potential as therapeutic targets.

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“…Whether GSTP1 and CLDNs playing significant roles in different biological characteristics of cancers is not clear, we hypothesize that there may be a close correlation in activity/function between CLDNs and GSTP1, which may provide a possible direction for cancer chemotherapy. Recently a study confirmed CLDN23 as a potential biomarker for the diagnosis and prognosis of gastric cancer, and it was further demonstrated that CLDN23 expression was positively correlated with GSTP1 activity in gastric cancer [ 19 ]. Abnormal high CLDN6 expression was found in MCF-7/MDR multidrug resistant breast cancer cells, however whether CLDN6 confers resistance to various anti-cancer drugs in this cell line need to be explored.…”

Section: Introductionmentioning

confidence: 99%

CLDN6 promotes chemoresistance through GSTP1 in human breast cancer

Yang

Shen

et al. 2017

J Exp Clin Cancer Res

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BackgroundClaudin-6 (CLDN6), a member of CLDN family and a key component of tight junction, has been reported to function as a tumor suppressor in breast cancer. However, whether CLDN6 plays any role in breast cancer chemoresistance remains unclear. In this study, we investigated the role of CLDN6 in the acquisition of chemoresistance in breast cancer cells.MethodsWe manipulated the expression of CLDN6 in MCF-7 and MCF-7/MDR cells with lv-CLDN6 and CLDN6-shRNA and investigated whether CLDN6 manipulation lead to different susceptibilities to several chemotherapeutic agents in these cells. The cytotoxicity of adriamycin (ADM), 5-fluorouracil (5-FU), and cisplatin (DDP) was tested by cck-8 assay. Cell death was determined by DAPI nuclear staining. The enzyme activity of glutanthione S-transferase-p1 (GSTP1) was detected by a GST activity kit. Then lv-GSTP1 and GSTP1-shRNA plasmids were constructed to investigate the potential of GSTP1 in regulating chemoresistance of breast cancer. The TP53-shRNA was adopted to explore the regulation mechanism of GSTP1. Finally, immunohistochemistry was used to explore the relationship between CLDN6 and GSTP1 expression in breast cancer tissues.ResultsSilencing CLDN6 increased the cytotoxicity of ADM, 5-FU, and DDP in MCF-7/MDR cells. Whereas overexpression of CLDN6 in MCF-7, the parental cell line of MCF-7/MDR expressing low level of CLDN6, increased the resistance to the above drugs. GSTP1 was upregulated in CLDN6-overexpressed MCF-7 cells. RNAi –mediated silencing of CLDN6 downregulated both GSTP1 expression and GST enzyme activity in MCF-7/MDR cells. Overexpresssion of GSTP1 in CLDN6 silenced MCF-7/MDR cells restored chemoresistance, whereas silencing GSTP1 reduced the chemoresistance due to ectopic overexpressed of CLDN6 in MCF-7 cells. These observations were also repeated in TNBC cells Hs578t. We further confirmed that CLDN6 interacted with p53 and promoted translocation of p53 from nucleus to cytoplasm, and both the expression and enzyme activity of GSTP1 were regulated by p53. Clinicopathologic analysis revealed that GSTP1 expression was positively associated with CLDN6 in human breast cancer samples.ConclusionHigh expression of CLDN6 confers chemoresistance on breast cancer which is mediated by GSTP1, the activity of which is regulated by p53. Our findings provide a new insight into mechanisms and strategies to overcome chemoresistance in breast cancer.Electronic supplementary materialThe online version of this article (10.1186/s13046-017-0627-9) contains supplementary material, which is available to authorized users.

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Expression of claudin-11, -23 in different gastric tissues and its relationship with the risk and prognosis of gastric cancer

Cited by 23 publications

References 39 publications

Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Differences in the expression profiles of claudin proteins in human gastric carcinoma compared with non‑neoplastic mucosa

Tight junction proteins in gastrointestinal and liver disease

CLDN6 promotes chemoresistance through GSTP1 in human breast cancer

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