Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12

Gröne, Jörn; Weber, Birgit; Staub, Eike; Heinze, M.; Klaman, Irina; Pilarsky, Christian; Hermann, K.; Castaños‐Vélez, Esmeralda; Röpcke, Stefan; Mann, B.; Rosenthal, André; Buhr, H. J.

doi:10.1007/s00384-006-0197-3

Cited by 81 publications

(84 citation statements)

References 29 publications

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“…Claudins, along with occludin, are essential structural elements of tight junctions, and constitute a family of 24 proteins that are important in carcinogenesis (6). The results of the current study were consistent with previous reports of upregulation of CLDN1 and CLDN2 (31)(32)(33)(34), and downregulation of CLDN8 (34) and CLDN23 (35) in tumor tissue compared with NC. A decrease in CLDN5 and CLDN15 levels was also identified in colorectal AD and AC, that had not previously been described.…”

Section: Discussionsupporting

confidence: 92%

Expression changes of cell-cell adhesion-related genes in colorectal tumors

et al. 2015

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Abstract. Epithelial tissues achieve a highly organized structure due to cell-cell junction complexes. Carcinogenesis is accompanied by changes in cell interactions and tissue morphology, which appear in the early stages of benign tumors and progress along with invasive potential. The aim of the present study was to analyze the changes in expression levels of genes encoding intercellular junction proteins that have been previously identified to be differentially expressed in colorectal tumors compared with normal mucosa samples (fold change, >2.5) in genome-wide expression profiling. The expression of 20 selected genes was assessed using quantitative reverse transcription polymerase chain reaction in 26 colorectal cancer, 42 adenoma and 24 normal mucosa samples. Between these tissue types, differences were observed in the mRNA levels of genes encoding adherens junction proteins (upregulation of CDH3 and CDH11, and downregulation of CDH19 and PTPRF), tight junction proteins (upregulation of CLDN1 and CLDN2, and downregulation of CLDN5, CLDN8, CLDN23, CLDN15, JAM2 and CGN) and desmosomes (upregulation of DSC3 and DSG3, and downregulation of DSC2), in addition to a decrease in the expression of certain other genes involved in intercellular connections: PCDHB14, PCDH7, MUPCDH and NEO1. The differences between tissue types were statistically significant, and separate clustering of normal adenoma and carcinoma samples was observed in a hierarchical clustering analysis. These results indicate that the morphological changes in neoplastic colon tissue that occur during the 'adenoma-carcinoma sequence' are accompanied by specific changes in the expression of multiple genes encoding the majority of cell-cell junction complexes. The particular differential expression patterns appear to be consistent among patients with cancer and adenoma, in addition to normal mucosa samples.

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Section: Discussionsupporting

confidence: 92%

Expression changes of cell-cell adhesion-related genes in colorectal tumors

et al. 2015

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“…Bioinformatic analysis demonstrated that CLDN8 was decreased in inflammatory bowel disease (Clark et al 2012). Moreover, the expression of CLDN8 mRNA is down-regulated in tumor tissues (Gröne et al 2007), and CLDN8 has been revealed as a candidate biomarker for the diagnosis in renal cell carcinoma and renal oncocytoma (Kim et al 2009;Osunkoya et al 2009). Recent research demonstrated CLDN8 functioned as an oncogenic factor and was up-regulated in OS cells ).…”

Section: Discussionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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Osteosarcoma is a malignant bone cancer that mainly affects children. SOX9 plays a key role in bone formation and osteosarcoma, and Claudin-8 (CLDN8), a tight junction protein, contributes to proliferation of osteosarcoma cells. The aim of this study was to investigate the relationship between SOX9 and CLDN8 in osteosarcoma. The expression levels of SOX9 and CLDN8 were determined in osteosarcoma specimens (n = 25) by qRT-PCR and Western blot analyses. The levels of SOX9 mRNA and protein were significantly higher in osteosarcoma tissues than those in adjacent non-tumor tissues, whereas the expression levels of CLDN8 mRNA and protein were significantly lower in osteosarcoma tissues. Immunohistochemical analysis showed the high expression of SOX9 in 56 out of 97 osteosarcoma tissues (57.7%). By contrast, the low expression of immunoreactive CLDN8 was observed in 62 of 97 osteosarcoma tissues (63.9%). There was the inverse correlation between the expression levels of SOX9 and CLDN8 proteins (R = −0.633, P < 0.001). The overall survival was poorer in the patients with high SOX9 expression. Subsequently, using two human osteosarcoma cell lines, we showed that knockdown of SOX9 inhibited cell proliferation and migration but promoted cell apoptosis. Importantly, knockdown of SOX9 increased the expression levels of CLDN8 protein. The transient luciferase-reporter assays suggest that SOX9 may inhibit the promoter activity of the CLDN8 gene in osteosarcoma cells. In conclusion, we provide the evidence demonstrating that SOX9 may promote cell growth by repressing the expression of CLDN8. Thus, SOX9 may be a therapeutic target for osteosarcoma.

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“…The expression of claudins-1, -3 and -4 was previously reported to be upregulated in human colorectal cancer (31). Furthermore, several studies have reported that the translocation of claudins is associated with tumor cell proliferation and survival (32,33). The expression of claudin-1 is upregulated in human colon cancers, particularly in the metastatic region, and is frequently mislocalized from the cell membrane to the cytoplasm and nucleus (19).…”

Section: Introductionmentioning

confidence: 98%

Nuclear expression of claudin‑3 in human colorectal adenocarcinoma cell lines and tissues

et al. 2017

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Abstract.Claudins are members of a large family of transmembrane proteins, which are essential for the formation of tight junctions and have a significant effect on the biological behavior of tumor progression. Previous studies have demonstrated that several claudins show aberrant expression patterns in numerous types of cancer. The present study investigated the expression and localization of claudin-3 and claudin-7 in human colorectal adenocarcinoma cell lines and tissues. The protein expression levels of claudin-3 and claudin-7 were determined using immunocytochemical and immunohistochemical staining. Claudin-3, but not claudin-7, exhibited nuclear localization in the human colorectal adenocarcinoma Caco-2 and SW620 cell lines. Surgically resected colorectal adenocarcinoma tissue specimens were obtained, and the associations between the expression of claudin-3 or claudin-7 and various clinicopathological parameters were analyzed. The membranous expression rates of claudin-3 and claudin-7 were 58.0 and 50.0%, while their nuclear expression rates were 22.0 and 2.0%, respectively. The membranous expression of claudin-3 and claudin-7 was not associated with any clinicopathological factors, whereas the nuclear expression of claudin-3 was associated with histological type and was significantly increased in colorectal mucinous adenocarcinomas compared with that in well-to moderately-differentiated colorectal adenocarcinomas (P<0.01). However, no associations were observed between the nuclear expression of claudin-7 and any clinicopathological parameter. In conclusion, the nuclear expression of claudin-3 in colorectal mucinous adenocarcinoma may be involved in the biological transformation of tumors. The results from the present study indicated that claudin-3 is an important protein associated with histological type and has potential as a prognostic marker. Although the mechanisms underlying the nuclear localization of claudin-3 in tumorigenesis have not yet been elucidated in detail, the present results indicated the potential of claudin-3 as a histopathological biomarker for colorectal adenocarcinomas.

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Differential expression of genes encoding tight junction proteins in colorectal cancer: frequent dysregulation of claudin-1, -8 and -12

Abstract: Differential expression of genes encoding claudins in CRC suggests that these tight junction proteins may be associated to and involved in tumorigenesis. CLDN1 is frequently up-regulated in large proportion of CRC and may represent potential target molecule for blocking studies in CRC.

Cited by 81 publications

References 29 publications

Expression changes of cell-cell adhesion-related genes in colorectal tumors

Expression changes of cell-cell adhesion-related genes in colorectal tumors

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Nuclear expression of claudin‑3 in human colorectal adenocarcinoma cell lines and tissues

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