title: Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.
abstract: We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion.
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Division of Oral Pathology, Department of Oral Basic and Clinical Sciences, College of Dentistry, Taibah University, Medina 41311, Saudi Arabia.
authors.forename: Hamzah
authors.initials: H
authors.lastname: Babkair
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan. Electronic address: manyamaz@dent.niigata-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yamazaki
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
authors.forename: Md Shihab
authors.initials: MS
authors.lastname: Uddin
authors.affiliation: Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Maruyama
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abé
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Essa
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Sumita
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
authors.forename: Md Shahidul
authors.initials: MS
authors.lastname: Ahsan
authors.affiliation: Division of Oral Pathology, Department of Oral Basic and Clinical Sciences, College of Dentistry, Taibah University, Medina 41311, Saudi Arabia.
authors.forename: Wael
authors.initials: W
authors.lastname: Swelam
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Division of Oral Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan; Oral Pathology Section, Department of Surgical Pathology, Niigata University Hospital, Niigata 951-8520, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saku
mesh_terms: D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D062445:Claudin-1 / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D019108:Tight Junctions / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1; D012333:RNA, Messenger; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein
keywords: Cell growth; Claudin-1; Invasion; Oral mucosa; Squamous cell carcinoma; Tight junction; Zonula occludens-1