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

Abstract

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.

Journal

Journal ID (nlm-ta): Cell Cycle

Journal ID (iso-abbrev): Cell Cycle

Journal ID (publisher-id): CC

Title: Cell Cycle

Publisher: Landes Bioscience

ISSN (Print): 1538-4101

ISSN (Electronic): 1551-4005

Publication date (Print): 15 May 2013

Publication date (Electronic): 17 April 2013

Publication date PMC-release: 17 April 2013

Volume: 12

Issue: 10

Pages: 1510-1520

Affiliations

[1 ]Department of Stem Cell Biology & Regenerative Medicine; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

[2 ]The Jefferson Stem Cell Biology and Regenerative Medicine Center; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

[3 ]Manchester Breast Centre & Breakthrough Breast Cancer Research Unit; Paterson Institute for Cancer Research; Institute of Cancer Sciences; Manchester Academic Health Science Centre; University of Manchester; Manchester, UK

[4 ]Department of Cancer Biology; Kimmel Cancer Center; Thomas Jefferson University; Philadelphia, PA USA

Author notes

[* ]Correspondence to: Michael P. Lisanti, Email: michaelp.lisanti@ 123456gmail.com and Jean-François Jasmin, Email: jeanfrancois.jasmin@ 123456gmail.com

Article

Publisher ID: 2013CC4888 Publisher Item ID: 24497

DOI: 10.4161/cc.24497

PMC ID: 3680531

PubMed ID: 23598719

Copyright statement: Copyright © 2013 Landes Bioscience

License:

This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

Categories

Subject: Report