Silencing of Eps8 blocks migration and invasion in human glioblastoma cell lines.
Glioblastoma multiforme (GBM) is the most malignant human primary brain tumor, and its infiltrative nature represents the leading cause for the failure of therapies and tumor recurrences. It is therefore crucial the knowledge of the molecular mechanisms underlying GBM invasion to identify novel therapeutic targets to limit motility. In this study, we evaluated the role of Epidermal growth factor receptor Pathway Substrate 8 (Eps8), a crucial regulator of the actin cytoskeleton dynamics accompanying cell motility and invasion, in GBM migration and invasiveness. We found that silencing of the protein by small interfering RNAs (siRNAs) abrogated the migratory and invasive capacity of three different human GBM cell lines both in 2-dimensional (2-D) and 3-dimensional (3-D) in vitro assays. The inhibitory effect on invasion was maintained independently by the migration mode utilized by the cells in our 3-D model, and was accompanied by an impaired formation of actin-based cytoskeletal protrusive structures. Our data propose Eps8 as a key molecule involved in the control of the intrinsic invasive behavior of GBM cells, and suggest that this protein might represent a useful target for the design of new drugs for the treatment of these tumors.
Department of Pharmacology, School of Medicine, Università degli Studi di Milano, Via Vanvitelli 32, 20129 Milano, Italy.
Maria Grazia
MG
Cattaneo
Elisa
E
Cappellini
Lucia M
LM
Vicentini
D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D034741:RNA, Small Interfering / Q000235:genetics; D018874:Spheroids, Cellular / Q000473:pathology; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; C489989:EPS8 protein, human; C107953:RAC1 protein, human; D034741:RNA, Small Interfering; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D020830:rac1 GTP-Binding Protein