title: Synaptopodin-2 induces assembly of peripheral actin bundles and immature focal adhesions to promote lamellipodia formation and prostate cancer cell migration.
abstract: Synaptopodin-2 (Synpo2), an actin-binding protein and invasive cancer biomarker, induces formation of complex stress fiber networks in the cell body and promotes PC3 prostate cancer cell migration in response to serum stimulation. The role of these actin networks in enhanced cancer cell migration is unknown. Using time-course analysis and live cell imaging of mock- and Synpo2-transduced PC3 cells, we now show that Synpo2 induces assembly of actin fibers near the cell periphery and Arp2/3-dependent lamellipodia formation. Lamellipodia formed in a non-directional manner or repeatedly changed direction, explaining the enhanced chemokinetic activity of PC3 cells in response to serum stimulation. Myosin contraction promotes retrograde flow of the Synpo2-associated actin filaments at the leading edge and their merger with actin networks in the cell body. Enhanced PC3 cell migration correlates with Synpo2-induced formation of lamellipodia and immature focal adhesions (FAs), but is not dependent on myosin contraction or FA maturation. The previously reported correlation between Synpo2-induced stress fiber assembly and enhanced PC3 cell migration therefore reflects the role of Synpo2 as a newly identified regulator of actin bundle formation and nascent FA assembly near the leading cell edge.
authors.affiliation: Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: FuiBoon
authors.initials: F
authors.lastname: Kai
authors.affiliation: Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.|Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: James P
authors.initials: JP
authors.lastname: Fawcett
authors.affiliation: Department of Microbiology & Immunology, Dalhousie University, Halifax, Nova Scotia, Canada.|Department of Biochemistry & Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada.|Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Roy
authors.initials: R
authors.lastname: Duncan
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051377:Actin-Related Protein 2 / Q000378:metabolism; D051378:Actin-Related Protein 3 / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D003599:Cytoskeleton / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011554:Pseudopodia / Q000378:metabolism / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D051377:Actin-Related Protein 2; D051378:Actin-Related Protein 3; D008840:Microfilament Proteins; D018994:Myosin Light Chains; D034741:RNA, Small Interfering; C503979:SYNPO2 protein, human
keywords: Synpo2; actin cytoskeleton; cancer cell migration; membrane protrusions; myopodin