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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Published in:Cell cycle (Georgetown, Tex.) Vol. 12; no. 10; pp. 1510 - 1520
Main Authors: Quann, Kevin, Gonzales, Donna M., Mercier, Isabelle, Wang, Chenguang, Sotgia, Federica, Pestell, Richard G., Lisanti, Michael P., Jasmin, Jean-François
Format: Journal Article
Language:English
Published: United States Taylor & Francis 15.05.2013
Landes Bioscience
Subjects:
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
Online Access:Get full text
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Summary: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.
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ISSN:1538-4101
1551-4005
1551-4005
DOI:10.4161/cc.24497