Caveolin-1 regulates glioblastoma aggressiveness through the control of alpha(5)beta(1) integrin expression and modulates glioblastoma responsiveness to SJ749, an alpha(5)beta(1) integrin antagonist.
Caveolin-1 plays a checkpoint function in the regulation of processes often altered in cancer. Although increased expression of caveolin-1 seems to be the norm in the glioma family of malignancies, populations of caveolin-1 positive and negative cells coexist among glioblastoma specimens. As no data are available to date on the contribution of such cells to the phenotype of glioblastoma, we manipulated caveolin-1 in the glioblastoma cell line U87MG. We showed that caveolin-1 plays a critical role in the aggressiveness of glioblastoma. We identified integrins as the main set of genes affected by caveolin-1. We reported here that the phenotypic changes observed after caveolin-1 modulation were mediated by alpha(5)beta(1) integrins. As a consequence of the regulation of alpha(5)beta(1) levels by caveolin-1, the sensitivity of cells to the specific alpha(5)beta(1) integrin antagonist, SJ749, was affected. Mediator of caveolin-1 effects, alpha(5)beta(1) integrin, is also a marker for glioma aggressiveness and an efficient target for the treatment of glioma especially the ones exerting the highest aggressive phenotype.
Martin
Sophie
S
Université Strasbourg 1 Institut Gilbert Laustriat, CNRS UMR 7175, Illkirch, France. Sophie.Martin@pharma.u-strasbg.fr
Cosset
Erika C
EC
Terrand
Jérôme
J
Maglott
Anne
A
Takeda
Ken
K
Dontenwill
Monique
M
D051242:Caveolin 1 / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis / Q000235:genetics; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D013141:Spiro Compounds / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D051242:Caveolin 1; D039081:Integrin alpha5beta1; D017395:Plasminogen Activator Inhibitor 1; D011422:Propionates; D011725:Pyridines; C512312:SJ749; D013141:Spiro Compounds; D020928:Mitogen-Activated Protein Kinases