Perturbation of the tight junction permeability barrier by occludin loop peptides activates beta-catenin/TCF/LEF-mediated transcription.
Here we show that interference with the integrity of the transepithelial permeability barrier of mouse mammary epithelial cells by treatment with synthetic peptides, homologous to the second extracellular domain of occludin, decreased the amount of occludin protein present at tight junctions and led to the formation of multilayered, unpolarized cell clusters. In addition, transcription of the adherens junction protein beta-catenin was induced. Following accumulation of soluble beta-catenin protein, transcription by beta-catenin/TCF/LEF was increased, as revealed by transcriptional assays following transient transfection of the reporter construct. Furthermore, treatment with occludin-II peptides up-regulated RNA levels of the known beta-catenin/TCF/LEF downstream target gene c-myc. The data presented imply a functional cross-talk between tight and adherens junctions that possibly contributes to the stepwise transformation during oncogenesis.
Vietor
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IMP, Institute of Molecular Pathology, Dr. Bohrgasse 7, A-1030 Vienna, Austria.
Bader
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T
Paiha
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Huber
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D000818:Animals; D015152:Blotting, Northern; D015820:Cadherins / Q000096:biosynthesis; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D016259:Genes, myc / Q000235:genetics; D008156:Luciferases / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1; D008321:Mammary Glands, Animal / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D062793:Occludin; D010455:Peptides / Q000494:pharmacology; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019108:Tight Junctions; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; D015820:Cadherins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051821:Lymphoid Enhancer-Binding Factor 1; D008565:Membrane Proteins; D062793:Occludin; C568986:Ocln protein, mouse; D010455:Peptides; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; D012313:RNA; D008156:Luciferases