The metabolic regulator ERRα, a downstream target of HER2/IGF-1, as a therapeutic target in breast cancer

A genomic signature designed to assess the activity of the estrogen-related receptor alpha (ERRα) was used to profile more than eight hundred breast tumors, revealing a shorter disease-free survival in patients with tumors exhibiting elevated receptor activity. Importantly, this signature also predi...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cancer cell 2011-10, Vol.20 (4), p.500-510
Hauptverfasser: Chang, Ching-yi, Kazmin, Dmitri, Jasper, Jeff S., Kunder, Rebecca, Zuercher, William J., McDonnell, Donald P.
Format: Artikel
Sprache:eng
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:A genomic signature designed to assess the activity of the estrogen-related receptor alpha (ERRα) was used to profile more than eight hundred breast tumors, revealing a shorter disease-free survival in patients with tumors exhibiting elevated receptor activity. Importantly, this signature also predicted the ability of an ERRα antagonist, XCT790, to inhibit proliferation in cellular models of breast cancer. Using a chemical genomic approach, it was determined that activation of the Her2/IGF-1 signaling pathways and subsequent C-MYC stabilization upregulate the expression of peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1β), an obligate cofactor for ERRα activity. PGC-1β knockdown in breast cancer cells impaired ERRα signaling and reduced cell proliferation, implicating a functional role for PGC1β/ERRα in the pathogenesis of breast cancers.
ISSN:1535-6108
1878-3686
DOI:10.1016/j.ccr.2011.08.023