title: Functional analysis of Zyxin in cell migration and invasive potential of oral squamous cell carcinoma cells.
abstract: Zyxin is an evolutionarily conserved protein that has been implicated in the regulation of actin assembly and is mainly located at focal adhesions. However, the biological roles of Zyxin in cancer cells are incompletely understood. We analyzed the functions of Zyxin in cell migration and the invasive potential of OSCC. Zyxin expression was examined using eight OSCC cell lines with two different cell morphologies (6 epithelial type and 2 fibroblastic type). To knockdown Zyxin expression, OSCC cells were transfected with Zyxin siRNA and control siRNA. The cell lines were studied by western blot analysis, immunocytochemical analysis and cell migration and invasion assay. Epithelial type OSCC cells showed a high level of E-cadherin expression and a low level of Zyxin expression. N-cadherin as well as Zyxin were strongly expressed in fibroblastic type OSCC cells. Expression levels of LPP and TRIP6, members of the human Zyxin family, did not differ between epithelial type and fibroblastic type. Knockdown of Zyxin expression by siRNA in fibroblastic type OSCC cells was associated with cell morphological changes from spindle (fibroblastic) to polygonal (epithelial) shape and significantly inhibited cell growth as well as cell migration and invasion. Expression levels of Rac1 and Cdc42 were weaker in Zyxin siRNA-treated fibroblastic type OSCC cells than in control siRNA-treated cells, but the expression of RhoA did not differ significantly. Treatment of fibroblastic type OSCC cells with Rac1 inhibitor decreased the expression of Zyxin mRNA and protein. Zyxin is suggested to promote growth, migration and invasiveness of fibroblastic type OSCC cells by upregulating Rac1 and Cdc42.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Hyogo College of                     Medicine, Nishinomiya, Hyogo 663-8501, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Yamamura
authors.forename: Kazuma
authors.initials: K
authors.lastname: Noguchi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Nakano
authors.forename: Emi
authors.initials: E
authors.lastname: Segawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Zushi
authors.forename: Kazuki
authors.initials: K
authors.lastname: Takaoka
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kishimoto
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hashimoto-Tamaoki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Urade
mesh_terms: D000074183:ATPases Associated with Diverse Cellular Activities; D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis; D017209:Apoptosis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D066246:ErbB Receptors / Q000096:biosynthesis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D060588:LIM Domain Proteins / Q000096:biosynthesis; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D046988:Proteasome Endopeptidase Complex; D011753:Pyrones / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering; D014157:Transcription Factors / Q000096:biosynthesis; D060589:Zyxin / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000096:biosynthesis*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015820:Cadherins; D003598:Cytoskeletal Proteins; C506907:EHT 1864; D060588:LIM Domain Proteins; C103594:LPP protein, human; C092282:PSMC5 protein, human; D011753:Pyrones; D011804:Quinolines; C107953:RAC1 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014157:Transcription Factors; D060589:Zyxin; C066737:RHOA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D046988:Proteasome Endopeptidase Complex; D000074183:ATPases Associated with Diverse Cellular Activities; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein