title: The role of drebrin in glioma migration and invasion.
abstract: Glioblastoma (GBM) is the most common primary brain tumor in adults. Despite current advances in therapy consisting of surgery followed by chemotherapy and radiation, the overall survival rate still remains poor. Therapeutic failures are partly attributable to the highly infiltrative nature of tumor adjacent to normal brain parenchyma. Recently, evidence is mounting to suggest that actin cytoskeleton dynamics are critical components of the cell invasion process. Drebrin is an actin-binding protein involved in the regulation of actin filament organization, and plays a significant role in cell motility; however, the role of drebrin in glioma cell invasiveness has not yet been fully elucidated. Therefore, this study was aimed to clarify the role of drebrin in glioma cell morphology and cell motility. Here we show that drebrin is expressed in glioma cell lines and in operative specimens of GBM. We demonstrate that stable overexpression of drebrin in U87 cells leads to alterations in cell morphology, and induces increased invasiveness in vitro while knockdown of drebrin in U87 cells by small interfering RNA (siRNA) decreases invasion and migration. In addition, we show that depletion of drebrin by siRNA alters glioma cell morphology in A172 GBM cell line. Our results suggest that drebrin contributes to the maintenance of cell shape, and may play an important role in glioma cell motility.
authors.affiliation: The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Terakawa
authors.forename: Sameer
authors.initials: S
authors.lastname: Agnihotri
authors.forename: Brian
authors.initials: B
authors.lastname: Golbourn
authors.forename: Mustafa
authors.initials: M
authors.lastname: Nadi
authors.forename: Nesrin
authors.initials: N
authors.lastname: Sabha
authors.forename: Christian A
authors.initials: CA
authors.lastname: Smith
authors.forename: Sidney E
authors.initials: SE
authors.lastname: Croul
authors.forename: James T
authors.initials: JT
authors.lastname: Rutka
mesh_terms: D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000235:genetics / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000494:pharmacology; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: D009479:Neuropeptides; D034741:RNA, Small Interfering; C053386:drebrins