title: Prostate cancer cell migration induced by myopodin isoforms is associated with formation of morphologically and biochemically distinct actin networks.
abstract: Myopodin is an actin-binding protein that promotes cancer cell migration in response to serum stimulation and is associated with invasive tumor development. To determine whether enhanced migration reflects changes in actin cytoskeleton remodeling, fluorescence confocal microscopy was used to examine the composition and morphology of filamentous actin structures in mock-transduced cells vs. stably transduced PC3 cells expressing human myopodin isoforms, and the chemokinetic response of cells was quantified using transwell assays. The same approaches were used to analyze the effects of external migration stimuli, actin polymerization inhibitors or deletion of the isoform-specific amino- and/or carboxy termini on cell migration and actin bundle formation. Results indicate that the termini of the myopodin isoforms differentially alter the formation of morphologically distinct F-actin networks that also differ in their myosin and myopodin staining patterns. Furthermore, enhanced cell migration was reduced by >50% when actin bundle formation was impaired by myopodin-truncation, low concentrations of an actin polymerization inhibitor, or in the absence of an external migration stimulus. Human myopodin isoforms are therefore potent regulators of stress fiber formation, inducing the formation of biochemically and morphologically distinct F-actin networks in the cell body whose presence directly correlates with increased cell migration.
authors.affiliation: 1Department of Microbiology and Immunology, Tupper Medical Bldg., 5850 College St., PO Box 15000, Dalhousie University, Halifax, NS, Canada, B3H 4R2. roy.duncan@dal.ca.
authors.forename: FuiBoon
authors.initials: F
authors.lastname: Kai
authors.forename: Roy
authors.initials: R
authors.lastname: Duncan
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D008840:Microfilament Proteins; D020033:Protein Isoforms; C503979:SYNPO2 protein, human
keywords: PC3 cells; actin bundles; actomyosin; stress fibers; synaptopodin 2