title: The motility of glioblastoma tumour cells is modulated by intracellular cofilin expression in a concentration-dependent manner.
abstract: The invasive behaviour of tumour cells has been attributed in part to dysregulated cell motility. Members of the ADF/Cofilin family of actin-binding proteins are known to increase microfilament dynamics by increasing the rate at which actin monomers leave the pointed end of the filament and by a filament-severing activity. As depolymerisation is a rate-limiting step in actin dynamics, ADF/Cofilins are suspected to facilitate the motility of cells. To test this, we investigated the influence of cofilin on tumour motility by transient and stably overexpressing cofilin in the human glioblastoma cell line, U373 MG. Several different methods were used to ascertain the level of cofilin in overexpressing clones and this was correlated with their rate of random locomotion. A biphasic relationship between cofilin level and locomotory rate was found. Clones that displayed a moderate amount of overproduction of cofilin were found to have increased rates of locomotion approximately linear to the overproduction of cofilin up to an optimal cofilin level of about 4.5 times that of wild type cells at which the cells were almost twice as fast. However, clones producing more than this optimal amount were found to locomote at progressively reduced speeds. Cells that overexpress cofilin have reduced stress fibres compared to control cells showing that the excess cofilin affects the actin cytoskeleton. We conclude that overexpression of cofilin enhances the motility of glioblastoma tumour cells in a concentration-dependent fashion, which is likely to contribute to their invasiveness.
authors.affiliation: Genes and Development Group, School of Biomedical and Clinical Laboratory Sciences, College of Medicine, University of Edinburgh, Scotland, United Kingdom.
authors.forename: Celestial T
authors.initials: CT
authors.lastname: Yap
authors.forename: T Ian
authors.initials: TI
authors.lastname: Simpson
authors.forename: Thomas
authors.initials: T
authors.lastname: Pratt
authors.forename: David J
authors.initials: DJ
authors.lastname: Price
authors.forename: Sutherland K
authors.initials: SK
authors.lastname: Maciver
mesh_terms: D051339:Actin Depolymerizing Factors; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation; D005909:Glioblastoma / Q000378:metabolism* / Q000648:ultrastructure; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D006801:Humans; D008840:Microfilament Proteins / Q000096:biosynthesis*; D018613:Microscopy, Confocal; D010957:Plasmids / Q000235:genetics; D014162:Transfection
chemical_list: D051339:Actin Depolymerizing Factors; D008840:Microfilament Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins