title: The impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness.
abstract: CLAUDIN-1 belongs to the family of transmembrane tight junction proteins tightening the paracellular cleft of epithelial cells. In human malignancies, CLAUDIN-1 is often dysregulated and located in subcellular compartments, particularly in the nucleus where it may influence cellular behaviour. Here, we studied CLAUDIN-1 in relation to the biological characteristics of follicular thyroid carcinoma (FTC). CLAUDIN-1 immuno-staining showed loss of membrane expression and increased nuclear CLAUDIN-1 localization in FTC metastases. CLAUDIN-1 function was further investigated in two different follicular thyroid carcinoma cell lines: FTC-133 isolated from a regional lymph node metastasis and FTC-238 derived from a lung metastasis. In both cell lines CLAUDIN-1 expression was demonstrated in the cell nuclei with a significantly higher protein expression in FTC-238 compared to FTC-133 cells. Interestingly, in vitro scratch assay revealed enriched nuclear CLAUDIN-1 expression near the scratch. Furthermore, the increase of the pathogenic character of FTC-133 cells by RASV12 transfection was associated with elevated CLAUDIN-1 expression and enhanced cell migration, invasion and proliferation. Likewise over-expression of nuclear CLAUDIN-1 in FTC-133 cells resulted in increased cell migration and invasion. Conversely, CLAUDIN-1 downregulation in FTC-238 cells by siRNA resulted in decreased cell migration and invasion and was accompanied by reduced phosphoPKC expression. Moreover, activation and inhibition of PKC resulted in CLAUDIN-1 up- and downregulation in FTC cells respectively. These data suggest an impact of CLAUDIN-1 on follicular thyroid carcinoma aggressiveness, which could potentially be influenced by PKC activity.
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany denise.zwanziger@uk-essen.de.
authors.forename: Denise
authors.initials: D
authors.lastname: Zwanziger
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Badziong
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Ting
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Lars Christian
authors.initials: LC
authors.lastname: Moeller
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Kurt Werner
authors.initials: KW
authors.lastname: Schmid
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Siebolts
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Wickenhauser
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.affiliation: Department of Endocrinology and Metabolism University Hospital Essen Institute of Pathology University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany Department of Pathology University Hospital Halle, Magdeburger Straße 14, 06097 Halle, Germany Department of General- Visceral- and Vascular Surgery, University Hospital Halle, Ernst-Grube-Straße 40, 06120 Halle, Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Fuehrer
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D062445:Claudin-1; D012333:RNA, Messenger; D011493:Protein Kinase C
keywords: CLAUDIN-1; nuclear localization; protein kinase C; thyroid carcinoma; tight junction; tumor aggressiveness; tumor biology