title: Pharmacological targeting of the constitutively activated MEK/MAPK-dependent signaling pathway in glioma cells inhibits cell proliferation and migration.
abstract: Activated mitogen-activated protein kinase MAPK cascade leading to ERK1/2 phosphorylation is expressed in the majority of glial neoplasms and negatively correlates with survival time of patients. Here we show that ERK1/2 kinases are constitutively activated in glioma cell lines and stem cell-enriched primary cultures of glioblastoma. Pharmacological targeting of the activated MEK/ERK1/2 module with the MEK inhibitor U0126 attenuates cell cycle progression (11 out of 11 cell lines), impairs single (7 out of 10) and collective cell migration (9 out of 11) and abolishes single cell emigration from monolayers (4 out of 9). Attacking the activated MEK/ERK1/2 module thus partially blocks the tumorigenic potential of glial cancer cells on different levels and strongly suggests the application of combination molecularly targeted therapies to interfere more efficiently with glial tumor development and progression.
authors.affiliation: Department of Anatomy, Anatomy and Cell Biology, University of Bonn, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Glassmann
authors.forename: Karl
authors.initials: K
authors.lastname: Reichmann
authors.forename: Björn
authors.initials: B
authors.lastname: Scheffler
authors.forename: Martin
authors.initials: M
authors.lastname: Glas
authors.forename: Nadine
authors.initials: N
authors.lastname: Veit
authors.forename: Rainer
authors.initials: R
authors.lastname: Probstmeier
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005910:Glioma / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051381:Rats
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D020929:Mitogen-Activated Protein Kinase Kinases