ARHGAP21 modulates FAK activity and impairs glioblastoma cell migration.
Glioblastoma multiforme is highly aggressive and is the most common glial tumor type. Although there have been advances in treatment, the average survival expectancy is 12-15 months. Several genes have been shown to influence glioblastoma progression. In the present work, we demonstrate that the RhoGTPase Activating Protein 21 (ARHGAP21) is expressed in the nuclear and perinuclear regions of several cell lines. In T98G and U138MG, glioblastoma derived cell lines, ARHGAP21 interacts with the C-terminal region of Focal Adhesion Kinase (FAK). ARHGAP21 depletion by shRNAi in T98G cells alters cellular morphology and increases: FAK phosphorylation states and activation of downstream signaling; the activity state of Cdc42; the production of metalloproteinase 2 (MMP-2) and cell migration rates. These modifications were found to be mainly due to the loss of ARHGAP21 action on FAK and, consequently, the activation of downstream effectors. These results suggest not only that ARHGAP21 might act as a tumor suppressor gene, but also indicate that ARHGAP21 might be a master regulator of migration having a crucial role in controlling the progression of different tumor types.
Bigarella
Carolina Louzão
CL
Department of Internal Medicine, School of Medical Science, Hematology and Hemotherapy Center-Hemocentro, University of Campinas-UNICAMP, Campinas, São Paulo 13083-970, Brazil. carolbiga@yahoo.com.br
Borges
Luciene
L
Costa
Fernando Ferreira
FF
Saad
Sara Terezinha Olalla
ST
D000199:Actins / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D050719:Crk-Associated Substrate Protein / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
C459590:ARHGAP21 protein, human; D000199:Actins; D050719:Crk-Associated Substrate Protein; D020690:GTPase-Activating Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D019061:src-Family Kinases; D020778:Matrix Metalloproteinase 2; D020764:cdc42 GTP-Binding Protein