Caveolin-1 is a negative regulator of tumor growth in glioblastoma and modulates chemosensitivity to temozolomide

Caveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using t...

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Vydáno v:	Cell cycle (Georgetown, Tex.) Ročník 12; číslo 10; s. 1510 - 1520
Hlavní autoři:	Quann, Kevin, Gonzales, Donna M., Mercier, Isabelle, Wang, Chenguang, Sotgia, Federica, Pestell, Richard G., Lisanti, Michael P., Jasmin, Jean-François
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Taylor & Francis 15.05.2013 Landes Bioscience
Témata:	Animals Apoptosis - drug effects Biomarkers, Tumor - metabolism brain cancer Brain Neoplasms - drug therapy Brain Neoplasms - metabolism Brain Neoplasms - pathology Caveolin 1 - genetics Caveolin 1 - metabolism Caveolin-1 Cell Line, Tumor chemotherapy Dacarbazine - analogs & derivatives Dacarbazine - pharmacology Dacarbazine - therapeutic use Down-Regulation Glioblastoma - drug therapy Glioblastoma - metabolism Glioblastoma - pathology glioma Humans Lentivirus - genetics Mice microarray Mitogen-Activated Protein Kinase 1 - metabolism Mitogen-Activated Protein Kinase 3 - metabolism mouse model Phosphatidylinositol 3-Kinases - metabolism Proto-Oncogene Proteins c-akt - metabolism Signal Transduction temozolomide TOR Serine-Threonine Kinases - metabolism Transplantation, Heterologous tumor progression tumor suppressor Caveolin-1 temozolomide microarray tumor progression mouse model glioma tumor suppressor brain cancer chemotherapy
ISSN:	1538-4101, 1551-4005, 1551-4005
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Shrnutí:	Caveolin-1 (Cav-1) is a critical regulator of tumor progression in a variety of cancers where it has been shown to act as either a tumor suppressor or tumor promoter. In glioblastoma multiforme, it has been previously demonstrated to function as a putative tumor suppressor. Our studies here, using the human glioblastoma-derived cell line U-87MG, further support the role of Cav-1 as a negative regulator of tumor growth. Using a lentiviral transduction approach, we were able to stably overexpress Cav-1 in U-87MG cells. Gene expression microarray analyses demonstrated significant enrichment in gene signatures corresponding to downregulation of MAPK, PI3K/AKT and mTOR signaling, as well as activation of apoptotic pathways in Cav-1-overexpressing U-87MG cells. These same gene signatures were later confirmed at the protein level in vitro. To explore the ability of Cav-1 to regulate tumor growth in vivo, we further show that Cav-1-overexpressing U-87MG cells display reduced tumorigenicity in an ectopic xenograft mouse model, with marked hypoactivation of MAPK and PI3K/mTOR pathways. Finally, we demonstrate that Cav-1 overexpression confers sensitivity to the most commonly used chemotherapy for glioblastoma, temozolomide. In conclusion, Cav-1 negatively regulates key cell growth and survival pathways and may be an effective biomarker for predicting response to chemotherapy in glioblastoma.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1538-4101 1551-4005 1551-4005
DOI:	10.4161/cc.24497