title: Overexpression of LASP-1 mediates migration and proliferation of human ovarian cancer cells and influences zyxin localisation.
abstract: LIM and SH3 protein 1 (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell proliferation and migration. In the present work, we analysed the effect of LASP-1 on biology and function of human ovarian cancer cell line SKOV-3 using small interfering RNA technique (siRNA). Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in SKOV-3 cells. The siRNA-treated cells were arrested in G(2)/M phase of the cell cycle and proliferation of the tumour cells was suppressed by 60-90% corresponding to around 70% of the cells being transfected successfully as seen by immunofluorescence. Moreover, transfected tumour cells showed a 40% reduced migration. LASP-1 silencing is accompanied by a reduced binding of the LASP-1-binding partner zyxin to focal contacts without changes in actin stress fibre and microtubule organisation or focal adhesion morphology as observed by immunofluorescence. In contrast, silencing of zyxin is not influencing cell migration and had neither influence on LASP-1 expression nor actin cytoskeleton and focal contact morphology suggesting that LASP-1 is necessary and sufficient for recruiting zyxin to focal contacts. The data provide evidence for an essential role of LASP-1 in tumour cell growth and migration, possibly through influencing zyxin localization.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, University of Wurzburg, Grombuehlstr. 12, D-97080 Wurzburg, Germany.
authors.forename: T G P
authors.initials: TG
authors.lastname: Grunewald
authors.forename: U
authors.initials: U
authors.lastname: Kammerer
authors.forename: C
authors.initials: C
authors.lastname: Winkler
authors.forename: D
authors.initials: D
authors.lastname: Schindler
authors.forename: A
authors.initials: A
authors.lastname: Sickmann
authors.forename: A
authors.initials: A
authors.lastname: Honig
authors.forename: E
authors.initials: E
authors.lastname: Butt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D016195:G2 Phase; D020868:Gene Silencing; D006019:Glycolysis; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering; D021241:Spectrometry, Mass, Electrospray Ionization; D060589:Zyxin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D006023:Glycoproteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D034741:RNA, Small Interfering; C092842:ZYX protein, human; D060589:Zyxin