Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells

Kyuno, Daisuke; Takasawa, Akira; Kikuchi, Satoshi; Takemasa, Ichiro; Osanai, Makoto; Kojima, Takashi

doi:10.1016/j.bbamem.2020.183503

Cited by 90 publications

(71 citation statements)

References 121 publications

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“…In addition, it is noteworthy that some of the deregulated pathways are associated with cancer. We observed an important negative correlation with the DNA repair complex [34], featuring six proteins integrating with this group, as well as a decrease in the cell-cell junction, including 58 proteins with a pivotal role in cancer progression [35]. Our results add new data to a previous study [12] in which a clear association between GC and DM was not found.…”

Section: Discussionsupporting

confidence: 72%

Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus

Osório

Silva

Ferreira

et al. 2021

JCM

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Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach—SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography—Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overrepresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell–cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer’s and Parkinson’s, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.

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Section: Discussionsupporting

confidence: 72%

Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus

Osório

Silva

Ferreira

et al. 2021

JCM

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“…TJs mainly consist of transmembrane proteins, including the cytoplasmic proteins, ZO-1, occludin, and claudins (61). Occludin have the cterminal coiled-coil domain, binds with ZO-1 to regulate intercellular signaling and message transmission, and affects actin contractility to control colonic permeability (62). Claudin, the main skeletal protein of TJs, is widely expressed in the basement membrane (63).…”

Section: Discussionmentioning

confidence: 99%

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis

Yan

et al. 2021

Front. Immunol.

145

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Intestinal microbiota dysbiosis is an established characteristic of ulcerative colitis (UC). Regulating the gut microbiota is an attractive alternative UC treatment strategy, considering the potential adverse effects of synthetic drugs used to treat UC. Kaempferol (Kae) is an anti-inflammatory and antioxidant flavonoid derived from a variety of medicinal plants. In this study, we determined the efficacy and mechanism of action of Kae as an anti-UC agent in dextran sulfate sodium (DSS)-induced colitis mice. DSS challenge in a mouse model of UC led to weight loss, diarrhea accompanied by mucous and blood, histological abnormalities, and shortening of the colon, all of which were significantly alleviated by pretreatment with Kae. In addition, intestinal permeability was shown to improve using fluorescein isothiocyanate (FITC)–dextran administration. DSS-induced destruction of the intestinal barrier was also significantly prevented by Kae administration via increases in the levels of ZO-1, occludin, and claudin-1. Furthermore, Kae pretreatment decreased the levels of IL-1β, IL-6, and TNF-α and downregulated transcription of an array of inflammatory signaling molecules, while it increased IL-10 mRNA expression. Notably, Kae reshaped the intestinal microbiome by elevating the Firmicutes to Bacteroidetes ratio; increasing the linear discriminant analysis scores of beneficial bacteria, such as Prevotellaceae and Ruminococcaceae; and reducing the richness of Proteobacteria in DSS-challenged mice. There was also an evident shift in the profile of fecal metabolites in the Kae treatment group. Serum LPS levels and downstream TLR4-NF-κB signaling were downregulated by Kae supplementation. Moreover, fecal microbiota transplantation from Kae-treated mice to the DSS-induced mice confirmed the effects of Kae on modulating the gut microbiota to alleviate UC. Therefore, Kae may exert protective effects against colitis mice through regulating the gut microbiota and TLR4-related signaling pathways. This study demonstrates the anti-UC effects of Kae and its potential therapeutic mechanisms, and offers novel insights into the prevention of inflammatory diseases using natural products.

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“…The function of cell adhesive junctions includes maintenance of the integrity of epithelial cells and regulation of signal communication between cells [26]. The downregulation of cell adhesion molecules is necessary for epithelial-mesenchymal transition (EMT), a process that facilitates the invasion and metastasis of cancer [26,27]. For mining regulators potentially responsible for KPNA4 upregulation, following protein-protein interaction analysis was performed with these genes associated with adherens junction and EMT.…”

Section: Discussionmentioning

confidence: 99%

“…Three primary molecular families: cadherins, armadillo proteins, and plakins constitute the adherens junction [26]. To a certain extent, the metastasis and epithelial-mesenchymal transition (EMT) of cancer cells are associated with loss of cell adhesion and increase of cellular mobility [26,27]. Therefore, we explored whether KPNA4 may impact the metastasis of PAAD or not.…”

Section: Translation Levels Of Kpnas In Patients With Paadmentioning

confidence: 99%

KPNA4 Serves as A Biomarker For Pancreatic Adnenocarcinoma KPNA4 Serves as A Promising Diagnostic and Prognostic Biomarker For Human Pancreatic Adenocarcinoma

Zhou

Zhu

Chu

et al. 2021

Preprint

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Objectives: Growing evidence suggests that aberrant expression of Karyopherin alpha (KPNA) has been involved in the tumor progression of various cancer types. However, the differential expression patterns and prognostic value of the seven KPNA subtypes remain to be investigated. Hence the transcriptional and survival data of KPNAs in patients with pancreatic adenocarcinoma (PAAD) were analyzed.Methods: Transcriptional and survival data related to KPNA expression in patients with PAAD were derived through ONCOMINE, Gene Expression Profiling Interactive Analysis 2, and Human protein atlas databases. The DNA alteration for KPNAs came from The Cancer Genome Atlas and c-BioPortal. The prognostic value analysis was performed with Kaplan–Meier Plotter. Gene functional enrichment analyses were conducted in database LinkedOmics and Metascape.Results: The mRNA expression levels of KPNA1-4, 6,7 were found significantly upregulated in pancreatic cancer tissues than in normal pancreas tissues, whereas the aberrant expression level of KPNA5 was no more significant in the former than in the latter. KPNA1, 4, and 7 were associated with tumor stage or grade of PAAD. Nevertheless, the obvious association with clinical outcomes was identified only in the aberrant expression of KPNA4. Further gene functional exploration about KPNA4 displayed KPNA4 strongly associated with adherens junction and tumor metastasis in PAAD. Conclusion: Our findings suggested that KPNA4 might be a potential diagnostic and a new biomarker of prognosis for patients with pancreatic adenocarcinoma.

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Role of tight junctions in the epithelial-to-mesenchymal transition of cancer cells

Cited by 90 publications

References 121 publications

Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus

Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus

Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-κB Axis

KPNA4 Serves as A Biomarker For Pancreatic Adnenocarcinoma KPNA4 Serves as A Promising Diagnostic and Prognostic Biomarker For Human Pancreatic Adenocarcinoma

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