The Metabolic Regulator ERRα, a Downstream Target of HER2/IGF-1R, As a Therapeutic Target in Breast Cancer

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2011 Oct 22

PMID 22014575

Citations 89

Authors

Ching-Yi Chang

Dmitri Kazmin

Jeff S Jasper

Rebecca Kunder

William J Zuercher

Donald P McDonnell

Affiliations

Soon will be listed here.

Abstract

A genomic signature designed to assess the activity of the estrogen-related receptor alpha (ERRα) was used to profile more than 800 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-1R 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 PGC-1β/ERRα in the pathogenesis of breast cancers.

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