title: Silencing of LASP-1 influences zyxin localization, inhibits proliferation and reduces migration in breast cancer cells.
abstract: LIM and SH3 protein (LASP-1), initially identified from human breast cancer, is a specific focal adhesion protein involved in cell migration. LASP-1 is an actin binding protein, which also interacts with the proline-rich domains of zyxin, a scaffolding protein required for cell movement and gene transcription. In the present work, we analyzed the effect of LASP-1 on different human breast cancer cell lines. Transfection with LASP-1-specific siRNA resulted in a reduced protein level of LASP-1 in BT-20 and MCF-7 cell lines. The siRNA-treated cells were arrested in G2/M phase of cell cycle, and proliferation of the tumor cells was suppressed by 30-50% corresponding to around 50% of the cells being transfected successfully as seen by immunofluorescence. In addition, tumor cells showed a 50% reduced migration after siRNA treatment, while overexpression of LASP-1 in non-tumor PTK-2 cells, which do not express endogenous LASP-1, resulted in a significant increase in cell motility. LASP-1 silencing is accompanied with a reduced binding of the of LASP-1 binding partner zyxin to focal contacts without changes in actin stress fiber organization as observed in immunofluorescence experiments. The data provide evidence for an essential role of LASP-1 in tumor cell growth and migration, possibly by influencing the localization of zyxin.
authors.affiliation: Institute of Clinical Biochemistry and Pathobiochemistry, University of Würzburg, Grombühlstr. 12, D-97080 Würzburg, Germany.
authors.forename: Thomas G P
authors.initials: TG
authors.lastname: Grunewald
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kammerer
authors.forename: Elfriede
authors.initials: E
authors.lastname: Schulze
authors.forename: Detlef
authors.initials: D
authors.lastname: Schindler
authors.forename: Arnd
authors.initials: A
authors.lastname: Honig
authors.forename: Michael
authors.initials: M
authors.lastname: Zimmer
authors.forename: Elke
authors.initials: E
authors.lastname: Butt
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D003598:Cytoskeletal Proteins; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020868:Gene Silencing; D006023:Glycoproteins / Q000378:metabolism*; D006131:Growth Inhibitors / Q000235:genetics* / Q000502:physiology; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D060589:Zyxin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D006131:Growth Inhibitors; D018398:Homeodomain Proteins; C096353:LASP1 protein, human; D060588:LIM Domain Proteins; D009363:Neoplasm Proteins; C092842:ZYX protein, human; D060589:Zyxin