Claudin-11 decreases the invasiveness of bladder cancer cells

Awsare, Ninaad; Martin, Tracey Amanda; Haynes, Mark D.; Matthews, P. N.; Jiang, Wen Guo

doi:10.3892/or.2011.1244

Cited by 18 publications

(10 citation statements)

References 16 publications

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“…Forced or silenced Cldn11 expression in cancer cells affects motility and invasiveness, indicating that Cldn11 may have a therapeutic role in preventing cancer progression 19 – 21 . Detection of promoter hypermethylation of Cldn11 can be used as a diagnostic parameter for distinguishing malignant melanoma from benign melanocytic lesions 22 , 23 .…”

Section: Discussionmentioning

confidence: 99%

Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling

et al. 2018

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Claudins (Cldns) are well-established components of tight junctions (TJs) that play a pivotal role in the modulation of paracellular permeability. Several studies have explored the physiologic aspects of Cldn family members in bone metabolism. However, the effect of Cldn11, a major component of central nervous system myelin, on bone homeostasis has not been reported. In this study, we demonstrate that Cldn11 is a potential target for bone disease therapeutics as a dual modulator of osteogenesis enhancement and osteoclastogenesis inhibition. We found that Cldn11 played a negative role in the receptor activator of nuclear factor kappa B ligand-induced osteoclast (OC) differentiation and function by downregulating the phosphorylated form of extracellular signal-regulated kinase (ERK), Bruton’s tyrosine kinase, and phospholipase C gamma 2, in turn impeding c-Fos and nuclear factor in activated T cell c1 expression. The enhancement of osteoblast (OB) differentiation by positive feedback of Cldn11 was achieved through the phosphorylation of Smad1/5/8, ERK, and c-Jun amino-terminal kinase. Importantly, this Cldn11-dependent dual event in bone metabolism arose from targeting EphrinB2 ligand reverse signaling in OC and EphB4 receptor forward signaling in OB. In agreement with these in vitro effects, subcutaneous injection of Cldn11 recombinant protein exerted anti-resorbing effects in a lipopolysaccharide-induced calvarial bone loss mouse model and increased osteogenic activity in a calvarial bone formation model. These findings suggest that Cldn11 is a novel regulator in bone homeostasis.

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Section: Discussionmentioning

confidence: 99%

Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling

et al. 2018

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“…If we take into account the set of validated miRNAs (upregulated miR-1228*, miR-3196, miR-1275, miR-1207 and downregulated miR-139-5p and miR-92b) we were able to detect in the literature their implications in escaping of apoptosis and therefore, contributing to migration and invasion [15,51-69]. Downregulation of one particular miRNA, miR-139, might promote gastric tumour progression and metastasis via upregulating CXCR4, Bao and cols suggest that miR-139 might be suppressed by upstream HER2 signaling, a strongly deregulated pathway in breast cancer [52].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA profile in very young women with breast cancer

et al. 2014

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BackgroundBreast cancer is rarely diagnosed in very young women (35years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients.MethodsWe performed a comprehensive study of miRNA expression using miRNA Affymetrix2.0 array on paraffin-embedded tumour tissue of 42 breast cancer patients 35 years old or younger, 17 patients between 45 and 65 years old and 29 older than 65 years. Data were statistically analyzed by t-test and a hierarchical clustering via average linkage method was conducted. Results were validated by qRT-PCR. Putative targeted pathways were obtained using DIANA miRPath online software.ResultsThe results show a differential and unique miRNA expression profile of 121 miRNAs (p-value <0.05), 96 of those with a FDR-value <0.05. Hierarchical clustering grouped the samples according to their age, but not by subtype nor by tumour characteristics. We were able to validate by qRT-PCR differences in the expression of 6 miRNAs: miR-1228*, miR-3196, miR-1275, miR-92b, miR-139 and miR-1207. Moreover, all of the miRNAs maintained the expression trend. The validated miRNAs pointed out pathways related to cell motility, invasion and proliferation.ConclusionsThe study suggests that breast cancer in very young women appears as a distinct molecular signature. To our knowledge, this is the first time that a validated microRNA profile, distinctive to breast cancer in very young women, has been presented. The miRNA signature may be relevant to open an important field of research in order to elucidate the underlying mechanism in this particular disease, which in a more clinical setting, could potentially help to identify therapeutic targets in this particular set of patients.

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“…Reduced CLDN11 expression is associated with increased invasiveness of gastric cancer cells [53]. Claudin-11 decreases the invasiveness of bladder cancer cells [103], and knockdown of claudin-11 in glioma stem cells promotes cell proliferation, supporting its tumor suppressor function [118]. …”

Section: Role Of Claudins In Human Cancermentioning

confidence: 99%

Emerging Roles of Claudins in Human Cancer

Kwon

2013

IJMS

186

177

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Claudins are major integral membrane proteins of tight junctions. Altered expression of several claudin proteins, in particular claudin-1, -3, -4 and -7, has been linked to the development of various cancers. Although their dysregulation in cancer suggests that claudins play a role in tumorigenesis, the exact underlying mechanism remains unclear. The involvement of claudins in tumor progression was suggested by their important role in the migration, invasion and metastasis of cancer cells in a tissue-dependent manner. Recent studies have shown that they play a role in epithelial to mesenchymal transition (EMT), the formation of cancer stem cells or tumor-initiating cells (CSCs/TICs), and chemoresistance, suggesting that claudins are promising targets for the treatment of chemoresistant and recurrent tumors. A recently identified claudin-low breast cancer subtype that is characterized by the enrichment of EMT and stem cell-like features is significantly associated with disease recurrence, underscoring the importance of claudins as predictors of tumor recurrence. The critical role of epigenetic mechanisms in the regulation of claudin expression indicates the possible application of epigenetic therapy to target claudins. A better understanding of the emerging role of claudins in CSC/TICs and chemoresistance may help to develop therapies against recurrent cancers.

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Claudin-11 decreases the invasiveness of bladder cancer cells

Cited by 18 publications

References 16 publications

Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling

Claudin 11 regulates bone homeostasis via bidirectional EphB4-EphrinB2 signaling

MicroRNA profile in very young women with breast cancer

Emerging Roles of Claudins in Human Cancer

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